TY - JOUR AU - Dittlau, K.S. AU - Chandrasekaran, A. AU - Freude, K. AU - Den, Bosch L.V. TI - Generation of Human Induced Pluripotent Stem Cell (hiPSC)-Derived Astrocytes for Amyotrophic Lateral Sclerosis and Other Neurodegenerative Disease Studies JF - BIO-PROTOCOL J2 - BIO-PROTOCOL VL - 14 PY - 2024 IS - 4 SN - 2331-8325 DO - 10.21769/BioProtoc.4936 UR - https://m2.mtmt.hu/api/publication/34779257 ID - 34779257 N1 - Department of Neurosciences, Experimental Neurology, Leuven Brain Institute, KU Leuven, University of Leuven, Leuven, Belgium Laboratory of Neurobiology, VIB Center for Brain & Disease Research, Leuven, Belgium Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark Export Date: 9 April 2024 Correspondence Address: Den Bosch, L.V.; Department of Neurosciences, Belgium; email: ludo.vandenbosch@kuleuven.be LA - English DB - MTMT ER - TY - JOUR AU - Matrella, M.L. AU - Valletti, A. AU - Gigante, I. AU - De, Rasmo D. AU - Signorile, A. AU - Russo, S. AU - Lobasso, S. AU - Lobraico, D. AU - Dibattista, M. AU - Pacelli, C. AU - Cocco, T. TI - High OXPHOS efficiency in RA-FUdr-differentiated SH-SY5Y cells: involvement of cAMP signalling and respiratory supercomplexes JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 14 PY - 2024 IS - 1 SN - 2045-2322 DO - 10.1038/s41598-024-57613-x UR - https://m2.mtmt.hu/api/publication/34779256 ID - 34779256 N1 - Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, 70124, Italy National Institute of Gastroenterology- IRCCS “Saverio De Bellis”, Via Turi 27, Castellana Grotte, Bari, 70013, Italy Bioenergetics and Molecular Biotechnologies, CNR-Institute of Biomembranes, Bari, 70124, Italy Department of Clinical and Experimental Medicine, University of Foggia, Foggia, 71122, Italy MASMEC Biomed S.p.A, Modugno, 70026, Italy Export Date: 9 April 2024 Correspondence Address: Cocco, T.; Department of Translational Biomedicine and Neuroscience, Italy; email: tizianamaria.cocco@uniba.it Correspondence Address: Pacelli, C.; Department of Clinical and Experimental Medicine, Italy; email: consiglia.pacelli@unifg.it LA - English DB - MTMT ER - TY - JOUR AU - Alsobaie, Sarah AU - Alsobaie, Tamador AU - Alshammary, Amal AU - Mantalaris, Sakis TI - Differentiation of human induced pluripotent stem cells into functional lung alveolar epithelial cells in 3D dynamic culture JF - FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY J2 - FRONT BIOENG BIOTECHNOL VL - 11 PY - 2023 PG - 13 SN - 2296-4185 DO - 10.3389/fbioe.2023.1173149 UR - https://m2.mtmt.hu/api/publication/34308807 ID - 34308807 N1 - Department of Clinical Laboratory Science, King Saud University, Riyadh, Saudi Arabia Biological Systems Engineering Laboratory, Department of Chemical Engineering, Imperial College London, London, United Kingdom Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, United States Export Date: 14 November 2023 Correspondence Address: Alsobaie, S.; Department of Clinical Laboratory Science, Saudi Arabia; email: salsobaie@ksu.edu.sa AB - Introduction: Understanding lung epithelium cell development from human induced pluripotent stem cells (IPSCs) in vitro can lead to an individualized model for lung engineering, therapy, and drug testing.Method: We developed a protocol to produce lung mature type I pneumocytes using encapsulation of human IPSCs in 1.1% (w/v) alginate solution within a rotating wall bioreactor system in only 20 days without using feeder cells. The aim was to reduce exposure to animal products and laborious interventions in the future.Results: The three-dimensional (3D) bioprocess allowed cell derivation into endoderm, and subsequently into type II alveolar epithelial cells within a very short period. Cells successfully expressed surfactant proteins C and B associated with type II alveolar epithelial cells, and the key structure of lamellar bodies and microvilli was shown by transmission electron microscopy. The survival rate was the highest under dynamic conditions, which reveal the possibility of adapting this integration for large-scale cell production of alveolar epithelial cells from human IPSCs.Discussion: We were able to develop a strategy for the culture and differentiation of human IPSCs into alveolar type II cells using an in vitro system that mimics the in vivo environment. Hydrogel beads would offer a suitable matrix for 3D cultures and that the high-aspect-ratio vessel bioreactor can be used to increase the differentiation of human IPSCs relative to the results obtained with traditional monolayer cultures. LA - English DB - MTMT ER - TY - JOUR AU - Buchner, Felix AU - Dokuzluoglu, Zeynep AU - Grass, Tobias AU - Rodriguez-Muela, Natalia TI - Spinal Cord Organoids to Study Motor Neuron Development and Disease JF - LIFE-BASEL J2 - LIFE-BASEL VL - 13 PY - 2023 IS - 6 PG - 38 SN - 2075-1729 DO - 10.3390/life13061254 UR - https://m2.mtmt.hu/api/publication/34308806 ID - 34308806 N1 - German Center for Neurodegenerative Diseases, Dresden, 01307, Germany Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, 01307, Germany Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, 01307, Germany Export Date: 14 November 2023 Correspondence Address: Rodriguez-Muela, N.; German Center for Neurodegenerative DiseasesGermany; email: natalia.rodriguez-muela@dzne.de AB - Motor neuron diseases (MNDs) are a heterogeneous group of disorders that affect the cranial and/or spinal motor neurons (spMNs), spinal sensory neurons and the muscular system. Although they have been investigated for decades, we still lack a comprehensive understanding of the underlying molecular mechanisms; and therefore, efficacious therapies are scarce. Model organisms and relatively simple two-dimensional cell culture systems have been instrumental in our current knowledge of neuromuscular disease pathology; however, in the recent years, human 3D in vitro models have transformed the disease-modeling landscape. While cerebral organoids have been pursued the most, interest in spinal cord organoids (SCOs) is now also increasing. Pluripotent stem cell (PSC)-based protocols to generate SpC-like structures, sometimes including the adjacent mesoderm and derived skeletal muscle, are constantly being refined and applied to study early human neuromuscular development and disease. In this review, we outline the evolution of human PSC-derived models for generating spMN and recapitulating SpC development. We also discuss how these models have been applied to exploring the basis of human neurodevelopmental and neurodegenerative diseases. Finally, we provide an overview of the main challenges to overcome in order to generate more physiologically relevant human SpC models and propose some exciting new perspectives. LA - English DB - MTMT ER - TY - JOUR AU - Castillo, Bautista C.M. AU - Sterneckert, J. TI - Progress and challenges in directing the differentiation of human iPSCs into spinal motor neurons JF - FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY J2 - FRONT CELL DEV BIOL VL - 10 PY - 2023 SN - 2296-634X DO - 10.3389/fcell.2022.1089970 UR - https://m2.mtmt.hu/api/publication/33688508 ID - 33688508 N1 - Export Date: 8 March 2023 Correspondence Address: Sterneckert, J.; Center for Regenerative Therapies TU Dresden (CRTD), Germany; email: jared.sterneckert@tu-dresden.de LA - English DB - MTMT ER - TY - JOUR AU - Esiyok, Nesil AU - Heide, Michael TI - The SVZ stem cell niche-components, functions, and in vitro modelling JF - FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY J2 - FRONT CELL DEV BIOL VL - 11 PY - 2023 PG - 10 SN - 2296-634X DO - 10.3389/fcell.2023.1332901 UR - https://m2.mtmt.hu/api/publication/34614913 ID - 34614913 AB - Neocortical development depends on the intrinsic ability of neural stem and progenitor cells to proliferate and differentiate to generate the different kinds of neurons in the adult brain. These progenitor cells can be distinguished into apical progenitors, which occupy a stem cell niche in the ventricular zone and basal progenitors, which occupy a stem cell niche in the subventricular zone (SVZ). During development, the stem cell niche provided in the subventricular zone enables the increased proliferation and self-renewal of basal progenitors, which likely underlie the expansion of the human neocortex. However, the components forming the SVZ stem cell niche in the developing neocortex have not yet been fully understood. In this review, we will discuss potential components of the SVZ stem cell niche, i.e., extracellular matrix composition and brain vasculature, and their possible key role in establishing and maintaining this niche during fetal neocortical development. We will also emphasize the potential role of basal progenitor morphology in maintaining their proliferative capacity within the stem cell niche of the SVZ. Finally, we will focus on the use of brain organoids to i) understand the unique features of basal progenitors, notably basal radial glia; ii) study components of the SVZ stem cell niche; and iii) provide future directions on how to improve brain organoids, notably the organoid SVZ, and make them more reliable models of human neocortical development and evolution studies. LA - English DB - MTMT ER - TY - JOUR AU - Gabriel, R. III AU - Boreland, A.J. AU - Pang, Z.P. TI - Whole Cell Patch Clamp Electrophysiology in Human Neuronal Cells JF - METHODS IN MOLECULAR BIOLOGY J2 - METHODS MOL BIOL VL - 2683 PY - 2023 SP - 259 EP - 273 PG - 15 SN - 1064-3745 DO - 10.1007/978-1-0716-3287-1_21 UR - https://m2.mtmt.hu/api/publication/34779260 ID - 34779260 N1 - Child Health Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, United States Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Piscataway, NJ, United States Export Date: 9 April 2024 Correspondence Address: Pang, Z.P.; Department of Neuroscience and Cell Biology, United States; email: pangzh@rwjms.rutgers.edu LA - English DB - MTMT ER - TY - JOUR AU - Gao, Haoyang AU - Sun, Chunhui AU - Shang, Shuo AU - Sun, Baojun AU - Sun, Mingyuan AU - Hu, Shuang AU - Yang, Hongru AU - Hu, Ying AU - Feng, Zhichao AU - Zhou, Weijia AU - Liu, Chao AU - Wang, Jingang AU - Liu, Hong TI - Wireless Electrical Signals Induce Functional Neuronal Differentiation of BMSCs on 3D Graphene Framework Driven by Magnetic Field JF - ACS NANO J2 - ACS NANO VL - 17 PY - 2023 IS - 16 SP - 16204 EP - 16220 PG - 17 SN - 1936-0851 DO - 10.1021/acsnano.3c05725 UR - https://m2.mtmt.hu/api/publication/34233644 ID - 34233644 N1 - Collaborative Innovation Center of Technology and Equipment for Biological Diagnosis and Therapy in Universities of Shandong, Institute for Advanced Interdisciplinary Research (iAIR), University of Jinan, Jinan, 250022, China State Key Laboratory of Crystal Materials, Shandong University, 27 Shandanan Road, Shandong, Jinan, 250100, China Cryomedicine Laboratory, Qilu Hospital, Shandong University, Jinan, 250012, China Cited By :2 Export Date: 9 April 2024 Correspondence Address: Sun, C.; Collaborative Innovation Center of Technology and Equipment for Biological Diagnosis and Therapy in Universities of Shandong, China; email: ifc_sunch@ujn.edu.cn Correspondence Address: Liu, C.; Cryomedicine Laboratory, China; email: qiluliuchao@sdu.edu.cn Correspondence Address: Wang, J.; Collaborative Innovation Center of Technology and Equipment for Biological Diagnosis and Therapy in Universities of Shandong, China; email: chm_wangjg@ujn.edu.cn Correspondence Address: Liu, H.; Collaborative Innovation Center of Technology and Equipment for Biological Diagnosis and Therapy in Universities of Shandong, China; email: hongliu@sdu.edu.cn AB - Bone marrow mesenchymal stem cells (BMSCs) are suggestedas candidatesfor neurodegeneration therapy by autologous stem cells to overcomethe lack of neural stem cells in adults. However, the differentiationof BMSCs into functional neurons is a major challenge for neurotherapy.Herein, a methodology has been proposed to induce functional neuronaldifferentiation of BMSCs on a conductive three-dimensional grapheneframework (GFs) combined with a rotating magnetic field. A wirelesselectrical signal of about 10 & mu;A can be generated on the surfaceof GFs by cutting the magnetic field lines based on the well-knownelectromagnetic induction effect, which has been proven to be suitablefor inducing neuronal differentiation of BMSCs. The enhanced expressionsof the specific genes/proteins and apparent Ca2+ intracellularflow indicate that BMSCs cultured on GFs with 15 min/day rotatingmagnetic field stimulation for 15 days can differentiate functionalneurons without any neural inducing factor. The animal experimentsconfirm the neural differentiation of BMSCs on GFs after transplantation in vivo, accompanied by stimulation of an external rotatingmagnetic field. This study overcomes the lack of autologous neuralstem cells for adult neurodegeneration patients and provides a facileand safe strategy to induce the neural differentiation of BMSCs, whichhas potential for clinical applications of neural tissue engineering. LA - English DB - MTMT ER - TY - JOUR AU - Hernaiz, Adelaida AU - Cobeta, Paula AU - Marin, Belen AU - Vazquez, Francisco Jose AU - Badiola, Juan Jose AU - Zaragoza, Pilar AU - Bolea, Rosa AU - Martin-Burriel, Inmaculada TI - Susceptibility of Ovine Bone Marrow-Derived Mesenchymal Stem Cell Spheroids to Scrapie Prion Infection JF - ANIMALS J2 - ANIMALS-BASEL VL - 13 PY - 2023 IS - 6 PG - 18 SN - 2076-2615 DO - 10.3390/ani13061043 UR - https://m2.mtmt.hu/api/publication/33918205 ID - 33918205 N1 - Laboratorio de Genética Bioquímica (LAGENBIO), Facultad de Veterinaria, Universidad de Zaragoza, IA2, IIS-Aragón, Zaragoza, 50013, Spain Centro de Encefalopatías y Enfermedades Transmisibles Emergentes (CEETE), Facultad de Veterinaria, Universidad de Zaragoza, IA2, IIS-Aragón, Zaragoza, 50013, Spain Equine Surgery and Medicine Service, Veterinary Hospital (HVUZ), Universidad de Zaragoza, Zaragoza, 50013, Spain Departamento de Patología Animal, Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, 50013, Spain Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, 28029, Spain Cited By :1 Export Date: 14 November 2023 Correspondence Address: Martín-Burriel, I.; Laboratorio de Genética Bioquímica (LAGENBIO), Spain; email: minma@unizar.es AB - Simple Summary Prion diseases are fatal and incurable neurodegenerative disorders affecting both humans and animals. The development of in vitro cellular models from naturally susceptible species such as ruminants can be very useful for the study of prion disease mechanisms and the discovery of potential therapies. Our study shows for the first time how the culture, in the form of three-dimensional spheroids of ovine mesenchymal stem cells derived from bone marrow in growth and neurogenic conditions, makes these cells more permissive to prion infection, mimicking the prion toxicity occurring in these diseases. This three-dimensional system appears as a potential in vitro model for studying prion diseases in a microenvironment approaching in vivo conditions. In neurodegenerative diseases, including prion diseases, cellular in vitro models appear as fundamental tools for the study of pathogenic mechanisms and potential therapeutic compounds. Two-dimensional (2D) monolayer cell culture systems are the most used cell-based assays, but these platforms are not able to reproduce the microenvironment of in vivo cells. This limitation can be surpassed using three-dimensional (3D) culture systems such as spheroids that more effectively mimic in vivo cell interactions. Herein, we evaluated the effect of scrapie prion infection in monolayer-cultured ovine bone marrow-derived mesenchymal stem cells (oBM-MSCs) and oBM-MSC-derived spheroids in growth and neurogenic conditions, analyzing their cell viability and their ability to maintain prion infection. An MTT assay was performed in oBM-MSCs and spheroids subjected to three conditions: inoculated with brain homogenate from scrapie-infected sheep, inoculated with brain homogenate from healthy sheep, and non-inoculated controls. The 3D conditions improved the cell viability in most cases, although in scrapie-infected spheroids in growth conditions, a decrease in cell viability was observed. The levels of pathological prion protein (PrPSc) in scrapie-infected oBM-MSCs and spheroids were measured by ELISA. In neurogenic conditions, monolayer cells and spheroids maintained the levels of PrPSc over time. In growth conditions, however, oBM-MSCs showed decreasing levels of PrPSc throughout time, whereas spheroids were able to maintain stable PrPSc levels. The presence of PrPSc in spheroids was also confirmed by immunocytochemistry. Altogether, these results show that a 3D culture microenvironment improves the permissiveness of oBM-MSCs to scrapie infection in growth conditions and maintains the infection ability in neurogenic conditions, making this model of potential use for prion studies. LA - English DB - MTMT ER - TY - JOUR AU - Imredy, John P. AU - Roussignol, Gautier AU - Clouse, Holly AU - Salvagiotto, Giorgia AU - Mazelin-Winum, Ludmilla TI - Comparative assessment of Ca2+ oscillations in 2- and 3-dimensional hiPSC derived and isolated cortical neuronal networks JF - JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS J2 - J PHARMACOL TOXICOL METH VL - 123 PY - 2023 IS - 1 PG - 16 SN - 1056-8719 DO - 10.1016/j.vascn.2023.107281 UR - https://m2.mtmt.hu/api/publication/34625559 ID - 34625559 N1 - In Vitro Safety Pharmacology, Merck & Co., Inc., Rahway, NJ, United States Preclinical Safety, Sanofi R&D, Montpellier, France Fujifilm Cellular Dynamics, Inc., Madison, WI, United States Cited By :1 Export Date: 9 April 2024 CODEN: JPTME Correspondence Address: Imredy, J.P.; Merck & Co., WP81-2207, 770 Sumneytown Pike, United States; email: john_imredy@merck.com LA - English DB - MTMT ER - TY - JOUR AU - Kim, Jong-Tae AU - Cho, Sung Min AU - Youn, Dong Hyuk AU - Hong, Eun Pyo AU - Park, Chan Hum AU - Lee, Younghyurk AU - Jung, Harry AU - Jeon, Jin Pyeong TI - Therapeutic effect of a hydrogel-based neural stem cell delivery sheet for mild traumatic brain injury JF - ACTA BIOMATERIALIA J2 - ACTA BIOMATER VL - 167 PY - 2023 SP - 335 EP - 347 PG - 13 SN - 1742-7061 DO - 10.1016/j.actbio.2023.06.027 UR - https://m2.mtmt.hu/api/publication/34308805 ID - 34308805 N1 - Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon, South Korea Department of Neurosurgery, Yonsei University Wonju College of Medicine, Wonju, South Korea Department of Neurosurgery, Hallym University College of Medicine, Chuncheon, South Korea Cited By :1 Export Date: 14 November 2023 Correspondence Address: Jeon, J.P.; Department of Neurosurgery, Gyo-dong, Chuncheon-si, South Korea; email: jjs6553@daum.net AB - Objective: There are no effective clinically applicable treatments for neuronal dysfunction after mild traumatic brain injury (TBI). Here, we evaluated the therapeutic effect of a new delivery method of mouse neural stem cell (mNSC) spheroids using a hydrogel, in terms of improvement in damaged cortical lesions and cognitive impairment after mild TBI. Methods: mNSCs were isolated from the subventricular zone and subgranular zone by a hydrogel-based culture system. GFP-transduced mNSCs were generated into spheroids and wrapped into a sheet for transplantation. Male C57BL/6J mice were randomly divided into four groups: sham operation, TBI, TBI with mNSC spheroids, and TBI with mNSC spheroid sheet transplantation covering the damaged cortex. Histopathological and immunohistochemical features and cognitive function were evaluated 7, 14, and 28 days after transplantation following TBI. Results: Hydrogel-based culture systems and mNSC isolation were successfully established from the adult mice. Essential transcription factors for NSCs, such as SOX2, PAX6, Olig2, nestin, and doublecortin (DCX), were highly expressed in the mNSCs. A transplanted hydrogel-based mNSC spheroid sheet showed good engraftment and survival ability, differentiated into TUJ1-positive neurons, promoted angiogenesis, and reduced neuronal degeneration. Also, TBI mice treated with mNSC spheroid sheet transplantation exhibited a significantly increased preference for a new object, suggesting improved cognitive function compared to the mNSC spheroids or no treatment groups. Conclusion: Transplantation with a hydrogel-based mNSC spheroid sheet showed engraftment, migration, and stability of delivered cells in a hostile microenvironment after TBI, resulting in improved cognitive function via reconstruction of the damaged cortex.Statement of Significance : This study presents the therapeutic effect of a new delivery method of mouse neural stem cells spheroids using a hydrogel, in terms of improvement in damaged cortical lesions and cognitive impairment after traumatic brain injury. Collagen/fibrin hydrogel allowed long-term survival and migratory ability of NSCs spheroids. Furthermore, transplanted hydrogel-based mNSCs spheroids sheet showed good engraftment, migration, and stability of delivered cells in a hostile microenvironment, resulting in reconstruction of the damaged cortex and improved cognitive function after TBI. Therefore, we suggest that a hydrogel-based mNSCs spheroids sheet could help to improve cognitive impairment after TBI.& COPY; 2023 The Authors. Published by Elsevier Ltd on behalf of Acta Materialia Inc.This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ) LA - English DB - MTMT ER - TY - JOUR AU - Lee, D. AU - Yang, K. AU - Xie, J. TI - Advances in Nerve Injury Models on a Chip JF - ADVANCED BIOLOGY J2 - ADV BIOL VL - 7 PY - 2023 IS - 8 SN - 2701-0198 DO - 10.1002/adbi.202200227 UR - https://m2.mtmt.hu/api/publication/33703588 ID - 33703588 N1 - Export Date: 16 March 2023 Correspondence Address: Xie, J.; Department of Surgery-Transplant and Mary and Dick Holland Regenerative Medicine Program, United States; email: jingwei.xie@unmc.edu LA - English DB - MTMT ER - TY - CHAP AU - Pravata, M.V. AU - Gressens, P. AU - Cappello, S. TI - Clinical and Molecular Overview of Cortical Malformations T2 - Neocortical Neurogenesis in Development and Evolution PB - Wiley SN - 9781119860808 T3 - Neocortical Neurogenesis in Development and Evolution PY - 2023 SP - 595 EP - 624 PG - 30 DO - 10.1002/9781119860914.ch27 UR - https://m2.mtmt.hu/api/publication/34327573 ID - 34327573 N1 - Export Date: 14 November 2023 LA - English DB - MTMT ER - TY - JOUR AU - Ren, Y. AU - Zhang, S. AU - Liang, Y. AU - Gong, Z. AU - Cui, Y. AU - Song, W. TI - Feeder cells treated with ethanol can be used to maintain self-renewal and pluripotency of human pluripotent stem cells JF - FEBS OPEN BIO J2 - FEBS OPEN BIO VL - 13 PY - 2023 IS - 2 SP - 279 EP - 292 PG - 14 SN - 2211-5463 DO - 10.1002/2211-5463.13538 UR - https://m2.mtmt.hu/api/publication/33703587 ID - 33703587 N1 - Export Date: 16 March 2023 Correspondence Address: Song, W.; School of Life Science and Engineering, Henan, China; email: songwei@hncj.edu.cn LA - English DB - MTMT ER - TY - CHAP AU - Sahin, A. AU - Ciki, B. AU - Karademir-Yilmaz, B. TI - In vitro evaluation of biomaterials for neural tissue engineering T2 - Biomaterials for Neural Tissue Engineering PB - Elsevier SN - 9780323906746 T3 - Biomaterials for Neural Tissue Engineering PY - 2023 SP - 367 EP - 415 PG - 49 DO - 10.1016/B978-0-323-90554-1.00003-3 UR - https://m2.mtmt.hu/api/publication/34327579 ID - 34327579 N1 - Genetic and Metabolic Diseases Research Center (GEMHAM), Marmara University, Istanbul, Turkey Department of Biochemistry, Faculty of Medicine, Marmara University, Istanbul, Turkey Export Date: 14 November 2023 LA - English DB - MTMT ER - TY - JOUR AU - Salcedo, Claudia AU - Pozo Garcia, Victoria AU - Garcia-Adan, Bernat AU - Ameen, Aishat O. AU - Gegelashvili, Georgi AU - Waagepetersen, Helle S. AU - Freude, Kristine K. AU - Aldana, Blanca I. TI - Increased glucose metabolism and impaired glutamate transport in human astrocytes are potential early triggers of abnormal extracellular glutamate accumulation in hiPSC-derived models of Alzheimer's disease JF - JOURNAL OF NEUROCHEMISTRY J2 - J NEUROCHEM PY - 2023 PG - 19 SN - 0022-3042 DO - 10.1111/jnc.16014 UR - https://m2.mtmt.hu/api/publication/34578064 ID - 34578064 AB - Glutamate recycling between neurons and astrocytes is essential to maintain neurotransmitter homeostasis. Disturbances in glutamate homeostasis, resulting in excitotoxicity and neuronal death, have been described as a potential mechanism in Alzheimer's disease (AD) pathophysiology. However, glutamate neurotransmitter metabolism in different human brain cells, particularly astrocytes, has been poorly investigated at the early stages of AD. We sought to investigate glucose and glutamate metabolism in AD by employing human induced pluripotent stem cell (hiPSC)-derived astrocytes and neurons carrying mutations in the amyloid precursor protein (APP) or presenilin-1 (PSEN-1) gene as found in familial types of AD (fAD). Methods such as live-cell bioenergetics and metabolic mapping using [C-13]-enriched substrates were used to examine metabolism in the early stages of AD. Our results revealed greater glycolysis and glucose oxidative metabolism in astrocytes and neurons with APP or PSEN-1 mutations, accompanied by an elevated glutamate synthesis compared to control WT cells. Astrocytes with APP or PSEN-1 mutations exhibited reduced expression of the excitatory amino acid transporter 2 (EAAT2), and glutamine uptake increased in mutated neurons, with enhanced glutamate release specifically in neurons with a PSEN-1 mutation. These results demonstrate a hypermetabolic phenotype in astrocytes with fAD mutations possibly linked to toxic glutamate accumulation. Our findings further identify metabolic imbalances that may occur in the early phases of AD pathophysiology. LA - English DB - MTMT ER - TY - JOUR AU - Salmanvandi, Mohsen AU - Haramshahi, Seyed Mohammad Amin AU - Mansouri, Elahe AU - Alizadeh, Akram TI - The Effect of Rosmarinic Acid on Neural Differentiation of Wartons Jelly-derived Mesenchymal Stem Cells in Two-dimensional and Three-dimensional Cultures using Chitosan-based Hydrogel JF - BASIC AND CLINICAL NEUROSCIENCE J2 - BASIC CLIN NEUROSCI VL - 14 PY - 2023 IS - 1 SP - 117 EP - 128 PG - 12 SN - 2008-126X DO - 10.32598/bcn.2021.2596.1 UR - https://m2.mtmt.hu/api/publication/33918202 ID - 33918202 N1 - Department of Material Engineerig, Najafabad Branch, Islamic Azad University, Najafabad, Iran Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran Department of Tissue Engineering & Regenerative Medicine, Faculty of AdvancedTechnologies in Medicine, Iran University of Medical Sciences, Tehran, Iran Laboratory of Research and Development of Tissue Engineering Products, HazratFatemeh hospital, Iran University of Medical Sciences, Tehran, Iran Department of Tissue engineering and Applied Cell Sciences, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran Export Date: 14 November 2023 Correspondence Address: Alizadeh, A.; Department of Tissue engineering and Applied Cell Sciences, Iran; email: alizadehbio@gmail.com AB - Introduction: Numerous studies have shown the positive effects of rosmarinic acid on the nervous system.Rosmarinic acid as a herbal compound with anti-inflammatory effects can prevent thedestructive effect of inflammation on the nervous system. Furthermore, various studies haveemphasized the advantages of three-dimensional (3D) culture over the two-dimensional (2D) culture of cells. Methods: In this study, thermosensitive chitosan (CH)-based hydrogel as a 3D scaffoldwith the combination of chitosan, beta-glycerol phosphate and hydroxyl ethyl cellulose (CH-GP-HEC) loaded with rosmarinic acid was used to induce neuronal differentiation in humanWharton jelly stem cells. Also, cells were divided into eight groups to evaluate the effect of 3Dcell culture and to compare gene expression in different induction conditions. Results: The results ofgene expression analysis showed the highest expression of neuronal markers in Whartons jelly derived mesenchymal stem cells (WJMSCs) cultured in chitosan, beta-glycerol phosphate and hydroxyl ethyl cellulose (ch-gp-hec) loaded with differentiation medium androsmarinic acid. According to the results of gene expression, rosmarinic acid alone has a positiveeffect on the induction of expression of neural markers. This positive effect is enhanced by cellculture in 3D conditions. Conclusion: This study shows that rosmarinic acid can be considered an inexpensiveand available compound for use in neural tissue engineering. The results of this study indicatethat rosmarinic acid can be considered a cheap and available compound for use in neural tissueengineering. LA - English DB - MTMT ER - TY - JOUR AU - Silva-Pedrosa, Rita AU - Salgado, Antonio Jose AU - Ferreira, Pedro Eduardo TI - Revolutionizing Disease Modeling: The Emergence of Organoids in Cellular Systems JF - CELLS J2 - CELLS-BASEL VL - 12 PY - 2023 IS - 6 PG - 28 SN - 2073-4409 DO - 10.3390/cells12060930 UR - https://m2.mtmt.hu/api/publication/33918204 ID - 33918204 N1 - Cited By :5 Export Date: 14 November 2023 Correspondence Address: Silva-Pedrosa, R.; Life and Health Sciences Research Institute (ICVS), Campus Gualtar, Portugal; email: id7588@alunos.uminho.pt AB - Cellular models have created opportunities to explore the characteristics of human diseases through well-established protocols, while avoiding the ethical restrictions associated with post-mortem studies and the costs associated with researching animal models. The capability of cell reprogramming, such as induced pluripotent stem cells (iPSCs) technology, solved the complications associated with human embryonic stem cells (hESC) usage. Moreover, iPSCs made significant contributions for human medicine, such as in diagnosis, therapeutic and regenerative medicine. The two-dimensional (2D) models allowed for monolayer cellular culture in vitro; however, they were surpassed by the three-dimensional (3D) cell culture system. The 3D cell culture provides higher cell-cell contact and a multi-layered cell culture, which more closely respects cellular morphology and polarity. It is more tightly able to resemble conditions in vivo and a closer approach to the architecture of human tissues, such as human organoids. Organoids are 3D cellular structures that mimic the architecture and function of native tissues. They are generated in vitro from stem cells or differentiated cells, such as epithelial or neural cells, and are used to study organ development, disease modeling, and drug discovery. Organoids have become a powerful tool for understanding the cellular and molecular mechanisms underlying human physiology, providing new insights into the pathogenesis of cancer, metabolic diseases, and brain disorders. Although organoid technology is up-and-coming, it also has some limitations that require improvements. LA - English DB - MTMT ER - TY - JOUR AU - Songsaad, A.T. AU - Thairat, S. AU - Seemaung, P. AU - Thongsuk, A. AU - Balit, T. AU - Ruangsawasdi, N. AU - Phruksaniyom, C. AU - Gonmanee, T. AU - White, K.L. AU - Thonabulsombat, C. TI - Characterization of neural stem cells derived from human stem cells from the apical papilla undergoing three-dimensional neurosphere induction JF - JOURNAL OF APPLIED ORAL SCIENCE J2 - J APPL ORAL SCI VL - 31 PY - 2023 SN - 1678-7757 DO - 10.1590/1678-7757-2023-0209 UR - https://m2.mtmt.hu/api/publication/34444712 ID - 34444712 N1 - Mahidol University, Faculty of Dentistry, Department of Anatomy, Bangkok, Thailand Mahidol University, Faculty of Dentistry, Oral Tissues, Cells and Molecular Biology Analysis and Research Center, Bangkok, Thailand Mahidol University, Faculty of Science, Department of Anatomy, Bangkok, Thailand Mahidol University, Faculty of Dentistry, Department of Pharmacology, Bangkok, Thailand Mahidol University, Faculty of Medicine, Ramathibodi Hospital, Chakri Naruebodindra Medical Institute, Samut Prakan, Thailand Utah State University, College of Agriculture and Applied Sciences, Department of Animal, Dairy, and Veterinary Sciences, Utah, United States Export Date: 19 December 2023 Correspondence Address: Thonabulsombat, C.; Mahidol University, 272 RAMA VI Road Ratchathewi, Thailand; email: charoensri.tho@mahidol.ac.th LA - English DB - MTMT ER - TY - JOUR AU - Xu, Xiaobing AU - Zhang, Huiting AU - Li, Jiahui AU - Chen, Yanyu AU - Zhong, Wangtao AU - Chen, Yanfang AU - Ma, Xiaotang TI - Combination of EPC-EXs and NPC-EXs with miR-126 and miR-210 overexpression produces better therapeutic effects on ischemic stroke by protecting neurons through the Nox2/ROS and BDNF/TrkB pathways JF - EXPERIMENTAL NEUROLOGY J2 - EXP NEUROL VL - 359 PY - 2023 PG - 15 SN - 0014-4886 DO - 10.1016/j.expneurol.2022.114235 UR - https://m2.mtmt.hu/api/publication/33238581 ID - 33238581 N1 - Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000, China Department of Pharmacology & Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45435, United States Export Date: 31 January 2023 CODEN: EXNEA Correspondence Address: Chen, Y.; Department of Pharmacology & Toxicology, United States AB - Backgrounds/aims: Neural progenitor cells (NPCs) and endothelial progenitor cell (EPCs) exhibit synergistical effects on protecting endothelial cell functions. MiR-126 and miR-210 can protect cell activities by regulating brain-derived neurotrophic factor (BDNF) and reactive oxygen species (ROS) production. Exosomes (EXs) mediate the beneficial effects of stem cells via delivering microRNAs (miRs). Here, we investigated the combi-nation effects of EXs from EPCs (EPC-EXs) and NPCs (NPC-EXs), and determined whether these EXs with miR-126 (EPC-EXsmiR-126) and miR-210 overexpression (NPC-EXsmiR-210) had better effects on hypoxia/reoxygenation (H/ R)-injured neurons and ischemic stroke (IS).Methods: Cultured neurons were subjected to hypoxia for 6 h and then co-cultured with culture medium, NPC-EXs, EPC-EXs, NPC-EXs + EPC-EXs or NPC-EXsmiR-210 + EPC-EXsmiR-126 under normoxia for 24 h. Cell apoptosis, ROS production, neurite outgrowth and BDNF level were analyzed. Permanent middle cerebral artery occlusion (MCAO) was performed on C57BL/6 mice to build IS model. The mice were injected with PBS or various EXs via tail vein 2 h after MCAO operation. After 24 h, infarct volume and neurological deficits score (NDS), neuronal apoptosis, ROS production and spine density of dendrites, and brain BDNF level were analyzed. For mechanism study, NADPH oxidase 2(Nox2) and BDNF receptor tyrosine kinase receptor B (TrkB) were determined, and TrkB inhibitor k-252a was used in in vitro and in vivo study.Results: 1) The level of miR-210 or miR-126 was increased after NPC-EXs or EPC-EXs treatment respectively. 2) In H/R-injured neurons, NPC-EXs or EPC-EXs decreased cell apoptosis and ROS production and promoted neurite outgrowth, which were associated with the downregulation of Nox2 and the increase of BDNF and p-TrkB/TrkB level. 3) In MCAO mice, NPC-EXs or EPC-EXs decreased infarct volume and NDS, reduced neural apoptosis and ROS production, and promoted the spine density of dendrites. The levels of Nox2, BDNF and p-TrkB/TrkB in mouse brain tissues changed in similar patterns as seen in the in vitro study. 4) In both cell and mouse models, combination of NPC-EXs and EPC-EXs was more effective than NPC-EXs or EPC-EXs alone on all of these effects. 5) EPC-EXsmiR-126 + NPC-EXsmiR-210 had better effects compared to NPC-EXs + EPC-EXs, which were inhibited by k-252a.Conclusion: EPC-EXsmiR-126 combined NPC-EXsmiR-210 further orchestrate the combinative protective effects of EPC-EXs and NPC-EXs on IS, possibly by protecting H/R-injured neurons through the Nox2/ ROS and BDNF/TrkB pathways. LA - English DB - MTMT ER - TY - JOUR AU - Yang, Xiaochun AU - Chen, Daichao AU - Sun, Qiushi AU - Wang, Yao AU - Xia, Yu AU - Yang, Jinyu AU - Lin, Chang AU - Dang, Xin AU - Cen, Zimu AU - Liang, Dongdong AU - Wei, Rong AU - Xu, Ze AU - Xi, Guangyin AU - Xue, Gang AU - Ye, Can AU - Wang, Li-Peng AU - Zou, Peng AU - Wang, Shi-Qiang AU - Rivera-Fuentes, Pablo AU - Puentener, Salome AU - Chen, Zhixing AU - Liu, Yi AU - Zhang, Jue AU - Zhao, Yang TI - A live-cell image-based machine learning strategy for reducing variability in PSC differentiation systems JF - CELL DISCOVERY J2 - CELL DISCOV VL - 9 PY - 2023 IS - 1 PG - 26 SN - 2056-5968 DO - 10.1038/s41421-023-00543-1 UR - https://m2.mtmt.hu/api/publication/34305217 ID - 34305217 AB - The differentiation of pluripotent stem cells (PSCs) into diverse functional cell types provides a promising solution to support drug discovery, disease modeling, and regenerative medicine. However, functional cell differentiation is currently limited by the substantial line-to-line and batch-to-batch variabilities, which severely impede the progress of scientific research and the manufacturing of cell products. For instance, PSC-to-cardiomyocyte (CM) differentiation is vulnerable to inappropriate doses of CHIR99021 (CHIR) that are applied in the initial stage of mesoderm differentiation. Here, by harnessing live-cell bright-field imaging and machine learning (ML), we realize real-time cell recognition in the entire differentiation process, e.g., CMs, cardiac progenitor cells (CPCs), PSC clones, and even misdifferentiated cells. This enables non-invasive prediction of differentiation efficiency, purification of ML-recognized CMs and CPCs for reducing cell contamination, early assessment of the CHIR dose for correcting the misdifferentiation trajectory, and evaluation of initial PSC colonies for controlling the start point of differentiation, all of which provide a more invulnerable differentiation method with resistance to variability. Moreover, with the established ML models as a readout for the chemical screen, we identify a CDK8 inhibitor that can further improve the cell resistance to the overdose of CHIR. Together, this study indicates that artificial intelligence is able to guide and iteratively optimize PSC differentiation to achieve consistently high efficiency across cell lines and batches, providing a better understanding and rational modulation of the differentiation process for functional cell manufacturing in biomedical applications. LA - English DB - MTMT ER - TY - JOUR AU - Zhao, J. AU - Yang, T. AU - Zhou, L. AU - Liu, J. AU - Mao, L. AU - Jia, R. AU - Zhao, F. TI - Porous gelatin microspheres implanted with adipose mesenchymal stromal cells promote angiogenesis via protein kinase B/endothelial nitric oxide synthase signaling pathway in bladder reconstruction JF - CYTOTHERAPY J2 - CYTOTHERAPY VL - 25 PY - 2023 IS - 12 SP - 1317 EP - 1330 PG - 14 SN - 1465-3249 DO - 10.1016/j.jcyt.2023.08.005 UR - https://m2.mtmt.hu/api/publication/34327575 ID - 34327575 N1 - Export Date: 14 November 2023 CODEN: CYTRF Correspondence Address: Jia, R.; Department of Urology, 68 Changle Road, China; email: ruipengj@163.com LA - English DB - MTMT ER - TY - JOUR AU - Ziai, Yasamin AU - Zargarian, Seyed Shahrooz AU - Rinoldi, Chiara AU - Nakielski, Pawel AU - Sola, Antonella AU - Lanzi, Massimiliano AU - Truong, Yen Bach AU - Pierini, Filippo TI - Conducting polymer-based nanostructured materials for brain-machine interfaces JF - WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY J2 - WIRES NANOMED NANOBI VL - 15 PY - 2023 IS - 5 PG - 33 SN - 1939-5116 DO - 10.1002/wnan.1895 UR - https://m2.mtmt.hu/api/publication/33918203 ID - 33918203 N1 - Department of Biosystems and Soft Matter, Institute of Fundamental Technological Research, Polish Academy of Sciences, Warsaw, Poland Commonwealth Scientific and Industrial Research Organisation (CSIRO), Manufacturing Business Unit, Clayton, VIC, Australia Department of Industrial Chemistry “Toso Montanari”, University of Bologna, Bologna, Italy Cited By :2 Export Date: 14 November 2023 Correspondence Address: Pierini, F.; Department of Biosystems and Soft Matter, Poland; email: fpierini@ippt.pan.pl AB - As scientists discovered that raw neurological signals could translate into bioelectric information, brain-machine interfaces (BMI) for experimental and clinical studies have experienced massive growth. Developing suitable materials for bioelectronic devices to be used for real-time recording and data digitalizing has three important necessitates which should be covered. Biocompatibility, electrical conductivity, and having mechanical properties similar to soft brain tissue to decrease mechanical mismatch should be adopted for all materials. In this review, inorganic nanoparticles and intrinsically conducting polymers are discussed to impart electrical conductivity to systems, where soft materials such as hydrogels can offer reliable mechanical properties and a biocompatible substrate. Interpenetrating hydrogel networks offer more mechanical stability and provide a path for incorporating polymers with desired properties into one strong network. Promising fabrication methods, like electrospinning and additive manufacturing, allow scientists to customize designs for each application and reach the maximum potential for the system. In the near future, it is desired to fabricate biohybrid conducting polymer-based interfaces loaded with cells, giving the opportunity for simultaneous stimulation and regeneration. Developing multi-modal BMIs, Using artificial intelligence and machine learning to design advanced materials are among the future goals for this field.This article is categorized under:Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease LA - English DB - MTMT ER - TY - JOUR AU - Beghin, A. AU - Grenci, G. AU - Sahni, G. AU - Guo, S. AU - Rajendiran, H. AU - Delaire, T. AU - Mohamad, Raffi S.B. AU - Blanc, D. AU - de, Mets R. AU - Ong, H.T. AU - Galindo, X. AU - Monet, A. AU - Acharya, V. AU - Racine, V. AU - Levet, F. AU - Galland, R. AU - Sibarita, J.-B. AU - Viasnoff, V. TI - Automated high-speed 3D imaging of organoid cultures with multi-scale phenotypic quantification JF - NATURE METHODS J2 - NAT METHODS VL - 19 PY - 2022 IS - 7 SP - 881 EP - 892 PG - 12 SN - 1548-7091 DO - 10.1038/s41592-022-01508-0 UR - https://m2.mtmt.hu/api/publication/33137051 ID - 33137051 N1 - Mechanobiology Institute, National University of Singapore, Singapore, Singapore Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Department of Microbiology and Immunology, National University of Singapore, Singapore, Singapore Biomedical Engineering Department, National University of Singapore, Singapore, Singapore University of Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR 5297, Bordeaux, France QuantaCell, Pessac, France University Bordeaux, CNRS, INSERM, Bordeaux Imaging Center, BIC, UAR 3420, US 4, Bordeaux, France Department of Biological Sciences, National University of Singapore, Singapore, Singapore IRL 3639 CNRS, Singapore, Singapore Cited By :1 Export Date: 11 October 2022 Correspondence Address: Beghin, A.; Mechanobiology Institute, Singapore; email: mbianne@nus.edu.sg Correspondence Address: Viasnoff, V.; Mechanobiology Institute, Singapore; email: dbsvvnr@nus.edu.sg Correspondence Address: Sibarita, J.-B.; University of Bordeaux, France; email: jean-baptiste.sibarita@u-bordeaux.fr LA - English DB - MTMT ER - TY - JOUR AU - Bierman-Duquette, R.D. AU - Safarians, G. AU - Huang, J. AU - Rajput, B. AU - Chen, J.Y. AU - Wang, Z.Z. AU - Seidlits, S.K. TI - Engineering Tissues of the Central Nervous System: Interfacing Conductive Biomaterials with Neural Stem/Progenitor Cells JF - ADVANCED HEALTHCARE MATERIALS J2 - ADV HEALTHC MATER VL - 11 PY - 2022 IS - 7 SN - 2192-2640 DO - 10.1002/adhm.202101577 UR - https://m2.mtmt.hu/api/publication/34776122 ID - 34776122 N1 - Department of Bioengineering, University of California Los Angeles, Los Angeles, 90095, United States David Geffen School of Medicine, University of California Los Angeles, Los Angeles, 90095, United States Export Date: 08 April 2024; Cited By: 14; Correspondence Address: S.K. Seidlits; Department of Bioengineering, University of California Los Angeles, Los Angeles, 90095, United States; email: seidlits@g.ucla.edu LA - English DB - MTMT ER - TY - JOUR AU - Bilkic, I. AU - Sotelo, D. AU - Anujarerat, S. AU - Ortiz, N.R. AU - Alonzo, M. AU - El, Khoury R. AU - Loyola, C.C. AU - Joddar, B. TI - Development of an extrusion-based 3D-printing strategy for clustering of human neural progenitor cells JF - HELIYON J2 - HELIYON VL - 8 PY - 2022 IS - 12 SN - 2405-8440 DO - 10.1016/j.heliyon.2022.e12250 UR - https://m2.mtmt.hu/api/publication/33703589 ID - 33703589 N1 - Department of Chemical Engineering and Materials Research Laboratory, University of California, Santa Barbara, CA 93106, United States Inspired Materials and Stem-Cell Based Tissue Engineering Laboratory (IMSTEL), The University of Texas at El Paso, El Paso, TX 79968, United States Department of Metallurgical, Materials, and Biomedical Engineering, M201 Engineering, The University of Texas at El Paso, 500 W. University Avenue, El Paso, TX 79968, United States Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79968, United States Border Biomedical Research Center, The University of Texas at El Paso, 500 W. University Avenue, El Paso, TX 79968, United States Export Date: 16 March 2023 Correspondence Address: Joddar, B.; Inspired Materials and Stem-Cell Based Tissue Engineering Laboratory (IMSTEL), United States; email: bjoddar@utep.edu LA - English DB - MTMT ER - TY - JOUR AU - Boutin, M.E. AU - Strong, C.E. AU - Van, Hese B. AU - Hu, X. AU - Itkin, Z. AU - Chen, Y.-C. AU - LaCroix, A. AU - Gordon, R. AU - Guicherit, O. AU - Carromeu, C. AU - Kundu, S. AU - Lee, E. AU - Ferrer, M. TI - A multiparametric calcium signal screening platform using iPSC-derived cortical neural spheroids. JF - SLAS DISCOVERY J2 - SLAS DISCOV PY - 2022 SN - 2472-5552 DO - 10.1016/j.slasd.2022.01.003 UR - https://m2.mtmt.hu/api/publication/33289472 ID - 33289472 N1 - Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, United States StemoniX, Inc, Maple Grove, MN, United States Ecovative Design, 70 Cohoes Avenue, Green Island, NY, United States Cited By :1 Export Date: 2 December 2022 Correspondence Address: Ferrer, M.; National Institutes of Health, 9800 Medical Center Dr, Building B, United States; email: marc.ferrer@nih.gov LA - English DB - MTMT ER - TY - JOUR AU - Branscome, Heather AU - Khatkar, Pooja AU - Al, Sharif Sarah AU - Yin, Dezhong AU - Jacob, Sheela AU - Cowen, Maria AU - Kim, Yuriy AU - Erickson, James AU - Brantner, Christine A. AU - El-Hage, Nazira AU - Liotta, Lance A. AU - Kashanchi, Fatah TI - Retroviral infection of human neurospheres and use of stem Cell EVs to repair cellular damage JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 12 PY - 2022 IS - 1 PG - 27 SN - 2045-2322 DO - 10.1038/s41598-022-05848-x UR - https://m2.mtmt.hu/api/publication/32789429 ID - 32789429 N1 - Funding Agency and Grant Number: National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [AI078859, AI074410, AI127351-01, AI043894, NS099029, R21DA050176, R01NS099029, R33 CA206937, R01AR068436]; Targeted Pharmaceuticals, LLC Funding text: We would like to thank all members of the Kashanchi lab for their contributions, especially Gwen Cox and interns Gabrielle Heller and Sahan Raghavan. We also would like express thanks to ATCC management, especially Drs. Mindy Goldsborough and James Kramer for supporting this work. This work was further supported by National Institutes of Health (NIH) Grants AI078859, AI074410, AI127351-01, AI043894, and NS099029 (to FK), R21DA050176 and R01NS099029 (to FK and LAL), and R33 CA206937 and R01AR068436 (to LAL). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Targeted Pharmaceuticals, LLC partially funded experiments related to 3D cultures and HIV-1 infections. AB - HIV-1 remains an incurable infection that is associated with substantial economic and epidemiologic impacts. HIV-associated neurocognitive disorders (HAND) are commonly linked with HIV-1 infection; despite the development of combination antiretroviral therapy (cART), HAND is still reported to affect at least 50% of HIV-1 infected individuals. It is believed that the over-amplification of inflammatory pathways, along with release of toxic viral proteins from infected cells, are primarily responsible for the neurological damage that is observed in HAND; however, the underlying mechanisms are not well-defined. Therefore, there is an unmet need to develop more physiologically relevant and reliable platforms for studying these pathologies. In recent years, neurospheres derived from induced pluripotent stem cells (iPSCs) have been utilized to model the effects of different neurotropic viruses. Here, we report the generation of neurospheres from iPSC-derived neural progenitor cells (NPCs) and we show that these cultures are permissive to retroviral (e.g. HIV-1, HTLV-1) replication. In addition, we also examine the potential effects of stem cell derived extracellular vesicles (EVs) on HIV-1 damaged cells as there is abundant literature supporting the reparative and regenerative properties of stem cell EVs in the context of various CNS pathologies. Consistent with the literature, our data suggests that stem cell EVs may modulate neuroprotective and anti-inflammatory properties in damaged cells. Collectively, this study demonstrates the feasibility of NPC-derived neurospheres for modeling HIV-1 infection and, subsequently, highlights the potential of stem cell EVs for rescuing cellular damage induced by HIV-1 infection. LA - English DB - MTMT ER - TY - JOUR AU - Elsafi Mabrouk, Mohamed H. AU - Goetzke, Roman AU - Abagnale, Giulio AU - Yesilyurt, Burcu AU - Salz, Lucia AU - Cypris, Olivia AU - Glück, Philipp AU - Liesenfelder, Sven AU - Zeevaert, Kira AU - Ma, Zhiyao AU - Toledo, Marcelo A.S. AU - Li, Ronghui AU - Costa, Ivan G. AU - Lampert, Angelika AU - Pachauri, Vivek AU - Schnakenberg, Uwe AU - Zenke, Martin AU - Wagner, Wolfgang TI - The spatial self-organization within pluripotent stem cell colonies is continued in detaching aggregates JF - BIOMATERIALS J2 - BIOMATERIALS VL - 282 PY - 2022 SN - 0142-9612 DO - 10.1016/j.biomaterials.2022.121389 UR - https://m2.mtmt.hu/api/publication/32789469 ID - 32789469 N1 - Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Aachen, 52074, Germany Institute for Biomedical Engineering – Cell Biology, RWTH Aachen University Medical School, Aachen, 52074, Germany St. Anna Children's Cancer Research Institute (CCRI), Zimmermannplatz 10Vienna 1090, Austria Institute of Pathology, RWTH Aachen University Medical School, Pauwelsstraße 30, Aachen, 52074, Germany Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, 52074, Germany Institute for Computational Genomics, RWTH Aachen University Medical School, Pauwelsstraße 19, Aachen, 52074, Germany Institute of Physiology, RWTH Aachen University Medical School, Pauwelsstraße 30, Aachen, 52074, Germany Institute of Materials in Electrical Engineering 1 and Chair of Micro-and Nanosystems, RWTH Aachen University, Aachen, 52074, Germany Cited By :2 Export Date: 11 October 2022 CODEN: BIMAD Correspondence Address: Elsafi Mabrouk, M.H.; Helmholtz-Institute for Biomedical Engineering, Germany; email: mmabrouk@ukaachen.de LA - English DB - MTMT ER - TY - JOUR AU - Francistiova, Linda AU - Vörös, Kinga AU - Lovász, Zsófia AU - Dinnyés, András AU - Kobolák, Julianna TI - Detection and Functional Evaluation of the P2X7 Receptor in hiPSC Derived Neurons and Microglia-Like Cells JF - FRONTIERS IN MOLECULAR NEUROSCIENCE J2 - FRONT MOL NEUROSCI VL - 14 PY - 2022 PG - 16 SN - 1662-5099 DO - 10.3389/fnmol.2021.793769 UR - https://m2.mtmt.hu/api/publication/32696786 ID - 32696786 N1 - Cited By :7 Export Date: 8 April 2024 Correspondence Address: Dinnyés, A.; Biotalentum LtdHungary; email: andras.dinnyes@biotalentum.hu LA - English DB - MTMT ER - TY - JOUR AU - Hall, Mikayla L. AU - Givens, Sophie AU - Santosh, Natasha AU - Iacovino, Michelina AU - Kyba, Michael AU - Ogle, Brenda M. TI - Laminin 411 mediates endothelial specification via multiple signaling axes that converge on beta-catenin JF - STEM CELL REPORTS J2 - STEM CELL REP VL - 17 PY - 2022 IS - 3 SP - 569 EP - 583 PG - 15 SN - 2213-6711 DO - 10.1016/j.stemcr.2022.01.005 UR - https://m2.mtmt.hu/api/publication/32789428 ID - 32789428 N1 - Funding Agency and Grant Number: National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 AR075413, R01 HL137204]; National Institutes of Health Stem Cell BiologyUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [T32 GM113846-09]; PACCS Division, Department of Medicine, University of Minnesota; National Science Foundation GRFPNational Science Foundation (NSF) Funding text: We would like to thank the Srivastava lab, University of California, San Francisco, for providing the miPSCs used in this study. We would also like to thank the Zhang Lab at the University of Alabama at Birmingham for providing the cell line hciPSC-MHCCCND2 (human cardiac fibroblast-derived induced pluripotent stem cells expressing cyclin D2 under the myosin heavy chain promoter) used for all hiPSC experiments. This research was funded by grants from National Institutes of Health R01 HL137204 to B.M.O.; National Institutes of Health R01 AR075413 to M.K.; National Institutes of Health Stem Cell Biology T32 GM113846-09 to M.L.H. Dinnaken Fellowship Funding by PACCS Division, Department of Medicine, University of Minnesota to M.L.H. and National Science Foundation GRFP to S.G. AB - The extracellular matrix (ECM) provides essential cues to promote endothelial specification during tissue development in vivo; correspondingly, ECM is considered essential for endothelial differentiation outside of the body. However, systematic studies to assess the precise contribution of individual ECM proteins to endothelial differentiation have not been conducted. Further, the multi-component nature of differentiation protocols makes it challenging to study the underlying mechanisms by which the ECM contributes to cell fate. In this study, we determined that Laminin 411 alone increases endothelial differentiation of induced pluripotent stem cells over collagen I or Matrigel. The effect of ECM was shown to be independent of vascular endothelial growth factor (VEGF) binding capacity. We also show that ECM-guided endothelial differentiation is dependent on activation of focal adhesion kinase (FAK), integrin-linked kinase (ILK), Notch, and beta-catenin pathways. Our results indicate that ECM contributes to endothelial differentiation through multiple avenues, which converge at the expression of active beta-catenin. LA - English DB - MTMT ER - TY - JOUR AU - Krumm, Johannes AU - Sekine, Keisuke AU - Samaras, Patroklos AU - Brazovskaja, Agnieska AU - Breunig, Markus AU - Yasui, Ryota AU - Kleger, Alexander AU - Taniguchi, Hideki AU - Wilhelm, Mathias AU - Treutlein, Barbara AU - Camp, J. Gray AU - Kuster, Bernhard TI - High temporal resolution proteome and phosphoproteome profiling of stem cell-derived hepatocyte development JF - CELL REPORTS J2 - CELL REP VL - 38 PY - 2022 IS - 13 SN - 2211-1247 DO - 10.1016/j.celrep.2022.110604 UR - https://m2.mtmt.hu/api/publication/32789453 ID - 32789453 N1 - Chair of Proteomics and Bioanalytics, Technical University of Munich, Freising, 85354, Germany Laboratory of Cancer Cell Systems, National Cancer Center Research Institute, Tokyo, 104-0045, Japan Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanagawa, Yokohama, 236-004, Japan Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, 04103, Germany Department of Internal Medicine I, Ulm University Hospital, Ulm, 89081, Germany Division of Regenerative Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan Computational Mass Spectrometry, Technical University of Munich, Freising, 85354, Germany Department of Biosystems Science and Engineering, ETH Zurich, Basel, 4058, Switzerland Institute of Molecular and Clinical Ophthalmology Basel, Basel, 4056, Switzerland Bavarian Biomolecular Mass Spectrometry Center (BayBioMS), Technical University of Munich, Freising, 85354, Germany Cited By :1 Export Date: 11 October 2022 Correspondence Address: Kuster, B.; Chair of Proteomics and Bioanalytics, Germany; email: kuster@tum.de LA - English DB - MTMT ER - TY - JOUR AU - Li, P. AU - Chen, Y. TI - Progress in Modeling Neural Tube Development and Defects by Organoid Reconstruction JF - NEUROSCIENCE BULLETIN J2 - NEUROSCI BULL VL - 38 PY - 2022 IS - 11 SP - 1409 EP - 1419 PG - 11 SN - 1673-7067 DO - 10.1007/s12264-022-00896-9 UR - https://m2.mtmt.hu/api/publication/33137059 ID - 33137059 N1 - Export Date: 11 October 2022 Correspondence Address: Chen, Y.; State Key Laboratory of Primate Biomedical Research and Institute of Primate Translational Medicine, China; email: chenyc@lpbr.cn LA - English DB - MTMT ER - TY - CHAP AU - Manfiolli, A.O. AU - Amaral, R. AU - Caliari-Oliveira, C. ED - Maria, H. Santana ED - Eliana, B. Souto ED - Ranjita, Shegokar TI - Stem cells, organoids, and cellular therapy T2 - Nanotechnology and Regenerative Medicine: History, Techniques, Frontiers, and Applications PB - Elsevier CY - Cham SN - 9780323904322 T3 - Nanotechnol. and Regenerative Medicine: History, Techniques, Frontiers, and Applications PY - 2022 SP - 233 EP - 263 PG - 31 DO - 10.1016/B978-0-323-90471-1.00003-7 UR - https://m2.mtmt.hu/api/publication/34327594 ID - 34327594 LA - English DB - MTMT ER - TY - JOUR AU - Merckx, N.L.L. AU - Van, Esch H. TI - Human Brain Models of Intellectual Disability: Experimental Advances and Novelties JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 12 SN - 1661-6596 DO - 10.3390/ijms23126476 UR - https://m2.mtmt.hu/api/publication/33137053 ID - 33137053 N1 - Laboratory of Stem Cell and Developmental Neurobiology, VIB-KU Leuven Center for Brain & Disease Research, Leuven, 3000, Belgium Center for Human Genetics, University Hospitals Leuven, Leuven, 3000, Belgium Laboratory for the Genetics of Cognition, Department of Human Genetics, KU Leuven—University of Leuven, Leuven, 3000, Belgium Export Date: 11 October 2022 Correspondence Address: Merckx, N.L.L.; Laboratory of Stem Cell and Developmental Neurobiology, Belgium; email: nona.merckx@kuleuven.be LA - English DB - MTMT ER - TY - JOUR AU - Mitrečić, Dinko AU - Hribljan, Valentina AU - Jagečić, Denis AU - Isaković, Jasmina AU - Lamberto, Federica AU - Horánszky, Alex Lajos AU - Zana, Melinda AU - Földes, Gábor AU - Zavan, Barbara AU - Pivoriūnas, Augustas AU - Martinez, Salvador AU - Mazzini, Letizia AU - Radenovic, Lidija AU - Milasin, Jelena AU - Chachques, Juan Carlos AU - Buzanska, Leonora AU - Song, Min Suk AU - Dinnyés, András TI - Regenerative Neurology and Regenerative Cardiology: Shared Hurdles and Achievements JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 2 PG - 20 SN - 1661-6596 DO - 10.3390/ijms23020855 UR - https://m2.mtmt.hu/api/publication/32616778 ID - 32616778 N1 - Laboratory for Stem Cells, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, 10000, Croatia Department of Histology and Embryology, University of Zagreb School of Medicine, Zagreb, 10000, Croatia Omnion Research International Ltd., Zagreb, 10000, Croatia BioTalentum Ltd., Aulich Lajos Str. 26, Gordillo, 2100, Hungary Department of Physiology and Animal Health, Institute of Physiology and Animal Health, Hungarian University of Agriculture and Life Sciences, Páter Károly Str. 1, Godollo, 2100, Hungary Heart and Vascular Center, Semmelweis University, Budapest, 1122, Hungary National Heart and Lung Institute, Imperial College London, London, W12 0NN, United Kingdom Department of Translational Medicine, University of Ferrara, Ferrara, 44121, Italy Department of Stem Cell Biology, State Research Institute Centre for Innovative Medicine, Vilnius, LT-01102, Lithuania Instituto de Neurociencias UMH-CSIC, San Juan de Alicante, 03550, Spain ALS Center, Department of Neurology, Maggiore della Carità Hospital, University of Piemonte Orientale, Novara, 28100, Italy Center for Laser Microscopy, Faculty of Biology, University of Belgrade, Belgrade, 11000, Serbia Laboratory for Stem Cell Research, School of Dental Medicine, University of Belgrade, Belgrade, 11000, Serbia Laboratory of Biosurgical Research, Pompidou Hospital, University of Paris, Paris, 75006, France Department of Stem Cell Bioengineering, Mossakowski Medical Research Institute Polish Academy of Sciences, Warsaw, 02-106, Poland HCEMM-USZ Stem Cell Research Group, Department of Cell Biology and Molecular Medicine, University of Szeged, Szeged, 6720, Hungary College of Life Sciences, Sichuan University, Chengdu, 610064, China Cited By :6 Export Date: 9 April 2024 Correspondence Address: Mitrečić, D.; Laboratory for Stem Cells, Croatia; email: dinko.mitrecic@mef.hr LA - English DB - MTMT ER - TY - JOUR AU - Nunes, Carolina AU - Singh, Pranika AU - Mazidi, Zahra AU - Murphy, Cormac AU - Bourguignon, Aurore AU - Wellens, Sara AU - Chandrasekaran, Vidya AU - Ghosh, Sreya AU - Zana, Melinda AU - Pamies, David AU - Thomas, Aurélien AU - Verfaillie, Catherine AU - Culot, Maxime AU - Dinnyés, András AU - Hardy, Barry AU - Wilmes, Anja AU - Jennings, Paul AU - Grillari, Regina AU - Grillari, Johannes AU - Zurich, Marie-Gabrielle AU - Exner, Thomas TI - An in vitro strategy using multiple human induced pluripotent stem cell-derived models to assess the toxicity of chemicals: A case study on paraquat JF - TOXICOLOGY IN VITRO J2 - TOXICOL IN VITRO VL - 81 PY - 2022 PG - 16 SN - 0887-2333 DO - 10.1016/j.tiv.2022.105333 UR - https://m2.mtmt.hu/api/publication/32696682 ID - 32696682 N1 - Department of Biomedical Sciences, University of Lausanne, Rue du Bugnon 7, Lausanne, 1005, Switzerland Swiss Centre for Applied Human Toxicology (SCAHT), University of Basel, Missionsstrasse 64, Basel, 4055, Switzerland Edelweiss Connect GmbH, Technology Park Basel, Hochbergerstrasse 60C, Basel, 4057, Switzerland Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, Basel, 4056, Switzerland Evercyte GmbH, Vienna, Austria Institute of Molecular Biotechnology, Department of Biotechnology, BOKU - University of Natural Resource and Life science (BOKU), Vienna, Austria Division of Molecular and Computational Toxicology, Department of Chemistry and Pharmaceutical Sciences, AIMMS, Vrije Universiteit Amsterdam, De Boelelaan 1108, Amsterdam, 1081 HZ, Netherlands BioTalentum Ltd, Gödöllő, Hungary Department of Physiology and Animal Health, Institute of Physiology and Animal Health, Hungarian University of Agriculture and Life Sciences, Gödöllõ, Hungary University of Artois, UR 2465, Laboratoire de la Barrière Hémato-Encéphalique (LBHE), Faculté des sciences Jean Perrin, Rue Jean Souvraz SP18, Lens, F-62300, France Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium Unit of Forensic Toxicology and Chemistry, CURML, Lausanne and Geneva University Hospitals, Geneva, Switzerland Faculty Unit of Toxicology, CURML, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland Department of Cell Biology and Molecular Medicine, University of Szeged, Szeged, Hungary Ludwig Boltzmann Institute for Traumatology Research Center in cooperation with AUVA, Vienna, Austria Seven Past Nine d.o.o., Hribljane 10, Cerknica, 1380, Slovenia Cited By :8 Export Date: 8 April 2024 CODEN: TIVIE Correspondence Address: Zurich, M.-G.; Department of Biomedical Sciences, Rue du Bugnon 7, Switzerland; email: mzurich@unil.ch LA - English DB - MTMT ER - TY - JOUR AU - Nunes, Carolina AU - Gorczyca, Gabriela AU - Mendoza-deGyves, Emilio AU - Ponti, Jessica AU - Bogni, Alessia AU - Carpi, Donatella AU - Bal-Price, Anna AU - Pistollato, Francesca TI - Upscaling biological complexity to boost neuronal and oligodendroglia maturation and improve in vitro developmental neurotoxicity (DNT) evaluation JF - REPRODUCTIVE TOXICOLOGY J2 - REPROD TOXICOL VL - 110 PY - 2022 SP - 124 EP - 140 PG - 17 SN - 0890-6238 DO - 10.1016/j.reprotox.2022.03.017 UR - https://m2.mtmt.hu/api/publication/32789460 ID - 32789460 N1 - Department of Biomedical Sciences, University of Lausanne, Lausanne, CH-1005, Switzerland Department of Endocrinology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University in Krakow, Kraków, Poland European Commission, Joint Research Centre (JRC), Ispra, Italy Cited By :2 Export Date: 11 October 2022 CODEN: REPTE Correspondence Address: Pistollato, F.; European Commission JRC, Via E. Fermi 2749, VA, Italy; email: francesca.pistollato@gmail.com LA - English DB - MTMT ER - TY - JOUR AU - O’Hara-Wright, M. AU - Mobini, S. AU - Gonzalez-Cordero, A. TI - Bioelectric Potential in Next-Generation Organoids: Electrical Stimulation to Enhance 3D Structures of the Central Nervous System JF - FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY J2 - FRONT CELL DEV BIOL VL - 10 PY - 2022 SN - 2296-634X DO - 10.3389/fcell.2022.901652 UR - https://m2.mtmt.hu/api/publication/33137056 ID - 33137056 N1 - Cited By :1 Export Date: 11 October 2022 Correspondence Address: Gonzalez-Cordero, A.; Stem Cell Medicine Group, Australia; email: agonzalez-cordero@cmri.org.au LA - English DB - MTMT ER - TY - JOUR AU - Palma-Tortosa, S. AU - Martínez-Curiel, R. AU - Aretio-Medina, C. AU - Avaliani, N. AU - Kokaia, Z. TI - Organotypic Cultures of Adult Human Cortex as an Ex vivo Model for Human Stem Cell Transplantation and Validation JF - JOVE-JOURNAL OF VISUALIZED EXPERIMENTS J2 - JOVE-J VIS EXP VL - 2022 PY - 2022 IS - 190 SN - 1940-087X DO - 10.3791/64234 UR - https://m2.mtmt.hu/api/publication/33703590 ID - 33703590 N1 - Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, Lund University, Sweden Lund Stem Cell Center, Lund University, Sweden Export Date: 16 March 2023 Correspondence Address: Palma-Tortosa, S.; Laboratory of Stem Cells and Restorative Neurology, Sweden; email: sara.palma_tortosa@med.lu.se LA - English DB - MTMT ER - TY - JOUR AU - Romero-Morales, A.I. AU - Gama, V. TI - Revealing the Impact of Mitochondrial Fitness During Early Neural Development Using Human Brain Organoids JF - FRONTIERS IN MOLECULAR NEUROSCIENCE J2 - FRONT MOL NEUROSCI VL - 15 PY - 2022 SN - 1662-5099 DO - 10.3389/fnmol.2022.840265 UR - https://m2.mtmt.hu/api/publication/32957710 ID - 32957710 N1 - Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, United States Vanderbilt Center for Stem Cell Biology, Vanderbilt University, Nashville, TN, United States Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, United States Export Date: 15 July 2022 Correspondence Address: Gama, V.; Department of Cell and Developmental Biology, United States; email: vivian.gama@vanderbilt.edu Chemicals/CAS: brain derived neurotrophic factor, 218441-99-7; fibroblast growth factor, 62031-54-3; retinoic acid, 302-79-4; transcription factor PAX6, 208996-75-2 Funding details: National Institutes of Health, NIH, 1R35GM128915-01, 1RF1MH123971-01 Funding text 1: Funding was provided by National Institutes of Health (NIH), with grants 1R35GM128915-01 and 1RF1MH123971-01 (VG). AB - Mitochondrial homeostasis -including function, morphology, and inter-organelle communication- provides guidance to the intrinsic developmental programs of corticogenesis, while also being responsive to environmental and intercellular signals. Two- and three-dimensional platforms have become useful tools to interrogate the capacity of cells to generate neuronal and glia progeny in a background of metabolic dysregulation, but the mechanistic underpinnings underlying the role of mitochondria during human neurogenesis remain unexplored. Here we provide a concise overview of cortical development and the use of pluripotent stem cell models that have contributed to our understanding of mitochondrial and metabolic regulation of early human brain development. We finally discuss the effects of mitochondrial fitness dysregulation seen under stress conditions such as metabolic dysregulation, absence of developmental apoptosis, and hypoxia; and the avenues of research that can be explored with the use of brain organoids. Copyright © 2022 Romero-Morales and Gama. LA - English DB - MTMT ER - TY - JOUR AU - Romero-Morales, Alejandra I. AU - Robertson, Gabriella L. AU - Rastogi, Anuj AU - Rasmussen, Megan L. AU - Temuri, Hoor AU - McElroy, Gregory Scott AU - Chakrabarty, Ram Prosad AU - Hsu, Lawrence AU - Almonacid, Paula M. AU - Millis, Bryan A. AU - Chandel, Navdeep S. AU - Cartailler, Jean-Philippe AU - Gama, Vivian TI - Human iPSC-derived cerebral organoids model features of Leigh syndrome and reveal abnormal corticogenesis JF - DEVELOPMENT J2 - DEVELOPMENT VL - 149 PY - 2022 IS - 20 PG - 20 SN - 0950-1991 DO - 10.1242/dev.199914 UR - https://m2.mtmt.hu/api/publication/33341431 ID - 33341431 N1 - Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, United States Feinberg School of Medicine, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, IL 60611, United States Creative Data Solutions, Vanderbilt Center for Stem Cell Biology, Vanderbilt University, Nashville, TN 37232, United States School of Economics and Finances, Universidad EAFIT, Colombia Vanderbilt Biophotonics Center, Vanderbilt University, Nashville, TN 37232, United States Feinberg School of Medicine, Department of Biochemistry and Molecular Genetics, Northwestern University, Chicago, IL 60611, United States Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232, United States Export Date: 9 April 2024 CODEN: DEVPE Correspondence Address: Gama, V.; Department of Cell and Developmental Biology, United States; email: vivian.gama@vanderbilt.edu AB - Leigh syndrome (LS) is a rare, inherited neurometabolic disorder that presents with bilateral brain lesions caused by defects in the mitochondrial respiratory chain and associated nuclear-encoded proteins. We generated human induced pluripotent stem cells (iPSCs) from three LS patient-derived fibroblast lines. Using whole-exome and mitochondrial sequencing, we identified unreported mutations in pyruvate dehydrogenase (GM0372, PDH; GM13411, MT-ATP6/PDH) and dihydrolipoyl dehydrogenase (GM01503, DLD). These LS patient-derived iPSC lines were viable and capable of differentiating into progenitor populations, but we identified several abnormalities in three-dimensional differentiation models of brain development. LS patient-derived cerebral organoids showed defects in neural epithelial bud generation, size and cortical architecture at 100 days. The double mutant MT-ATP6/PDH line produced organoid neural precursor cells with abnormal mitochondrial morphology, characterized by fragmentation and disorganization, and showed an increased generation of astrocytes. These studies aim to provide a comprehensive phenotypic characterization of available patient -derived cell lines that can be used to study Leigh syndrome. LA - English DB - MTMT ER - TY - JOUR AU - Wang, Tao AU - Han, Yang AU - Wu, Zejia AU - Qiu, Shuai AU - Rao, Zilong AU - Zhao, Cailing AU - Zhu, Qingtang AU - Quan, Daping AU - Bai, Ying AU - Liu, Xiaolin TI - Tissue-Specific Hydrogels for Three-Dimensional Printing and Potential Application in Peripheral Nerve Regeneration JF - TISSUE ENGINEERING PART A J2 - TISSUE ENG PT A VL - 28 PY - 2022 IS - 3-4 SP - 161 EP - 174 PG - 14 SN - 1937-3341 DO - 10.1089/ten.tea.2021.0093 UR - https://m2.mtmt.hu/api/publication/32789430 ID - 32789430 N1 - Guangdong Peripheral Nerve Tissue Engineering and Technology Research Center, Department of Orthopedic and Microsurgery, First Affiliated Hospital, Sun Yat-sen University, No.135 Xin'gangxi Road, Guangzhou, 510275, China Guangdong Provincial Soft Tissue Biofabrication Engineering Laboratory, Guangzhou, China Department of Obstetrics, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China PCFM Lab, School of Chemistry, Sun Yat-sen University, Guangzhou, China Guangdong Functional Biomaterials Engineering Technology Research Center, School of Materials Science and Engineering, Sun Yat-sen University, No. 58 Zhongshan Er Road, Guangzhou, 510080, China Cited By :2 Export Date: 11 October 2022 Correspondence Address: Liu, X.; Guangdong Peripheral Nerve Tissue Engineering and Technology Research Center, No.135 Xin'gangxi Road, China; email: gzxiaolinliu@hotmail.com Correspondence Address: Bai, Y.; Guangdong Functional Biomaterials Engineering Technology Research Center, No. 58 Zhongshan Er Road, China; email: baiy28@mail.sysu.edu.cn AB - Impact statementTissue-derived decellularized matrices have drawn broad interests for their versatile applications in tissue engineering and regenerative medicine, especially the decellularized peripheral nerve matrix, which can effectively facilitate axonal extension, remyelination, and neural functional restoration after peripheral nerve injury. However, neither decellularized porcine nerve matrix (pDNM) nor pDNM hydrogel (pDNM-G) can be directly used in three-dimensional printing for personalized nerve constructs or cell transplantation. This work developed a hybrid hydrogel consisting of decellularized extracellular matrix hydrogel (dECM-G) and photocrosslinkable gelatin methacrylate (GelMA), which resulted in significantly improved printability and structural fidelity. The GelMA/pDNM-G hydrogel retained high bioactivity and tissue-specificity due to its dECM-G content. Such hybrid hydrogel systems built up a springboard in advanced biomaterials for neural tissue engineering, as well as a promising strategy for dECM containing bioprinting. Decellularized extracellular matrix hydrogel (dECM-G) has demonstrated its significant tissue-specificity, high biocompatibility, and versatile utilities in tissue engineering. However, the low mechanical stability and fast degradation are major drawbacks for its application in three-dimensional (3D) printing. Herein, we report a hybrid hydrogel system consisting of dECM-Gs and photocrosslinkable gelatin methacrylate (GelMA), which resulted in significantly improved printability and structural fidelity. These premixed hydrogels retained high bioactivity and tissue-specificity due to their containing dECM-Gs. More specifically, it was realized that the hydrogel containing dECM-G derived from porcine peripheral nerves (GelMA/pDNM-G) effectively facilitated neurite growth and Schwann cell migration from two-dimensional cultured dorsal root ganglion explants. The nerve cells were also encapsulated in the GelMA/pDNM-G hydrogel for 3D culture or underwent cell-laden bioprinting with high cell viability. The preparation of such GelMA/dECM-G hydrogels enabled the recapitulation of functional tissues through extrusion-based bioprinting, which holds great potential for applications in regenerative medicine. LA - English DB - MTMT ER - TY - CHAP AU - Wongtrakoongate, Patompon AU - Pakiranay, Chatbenja AU - Kitiyanant, Narisorn ED - Yahaya, Badrul Hisham TI - Toward Understanding Neurodegeneration Using Brain Organoids T2 - Organoid Technology for Disease Modelling and Personalized Treatment PB - Springer Netherlands CY - Cham SN - 9783030930554 T3 - Stem Cell Biology and Regenerative Medicine, ISSN 2196-8985 ; 71. PY - 2022 SP - 91 EP - 107 PG - 17 DO - 10.1007/978-3-030-93056-1_5 UR - https://m2.mtmt.hu/api/publication/32789437 ID - 32789437 LA - English DB - MTMT ER - TY - JOUR AU - Amponsah, Asiamah Ernest AU - Guo, Ruiyun AU - Kong, Desheng AU - Feng, Baofeng AU - He, Jingjing AU - Zhang, Wei AU - Liu, Xin AU - Du, Xiaofeng AU - Ma, Zhenhuan AU - Liu, Boxin AU - Ma, Jun AU - Cui, Huixian TI - Patient-derived iPSCs, a reliable in vitro model for the investigation of Alzheimer's disease JF - REVIEWS IN THE NEUROSCIENCES J2 - REV NEUROSCI VL - 32 PY - 2021 IS - 4 SP - 379 EP - 402 PG - 24 SN - 0334-1763 DO - 10.1515/revneuro-2020-0065 UR - https://m2.mtmt.hu/api/publication/32287697 ID - 32287697 N1 - Funding Agency and Grant Number: Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81801278]; Natural Science Foundation of Hebei ProvinceNatural Science Foundation of Hebei Province [H2019206637]; China Scholarship CouncilChina Scholarship Council [201608130015]; Hebei University Science And Technology Research Project [ZD2019049]; Excellent Overseas researcher Program in Hebei Provincial Department of Human Resources and Social Security [C20190509]; Key Natural Science Foundation of Hebei Province [H2020206557] Funding text: This work was supported by Natural Science Foundation of China (Grant No. 81801278), Natural Science Foundation of Hebei Province (Grant No. H2019206637), China Scholarship Council (Grant No. 201608130015), Hebei University Science And Technology Research Project (Grant No. ZD2019049), Excellent Overseas researcher Program in Hebei Provincial Department of Human Resources and Social Security (Grant No. C20190509), Key Natural Science Foundation of Hebei Province (Grant No. H2020206557). AB - Alzheimer's disease (AD) is a neurodegenerative disease and a common cause of dementia among elderly individuals. The disease is characterized by progressive cognitive decline, accumulation of senile amyloid plaques and neurofibrillary tangles, oxidative stress, and inflammation. Human-derived cell models of AD are scarce, and over the years, non-human-derived models have been developed to recapitulate clinical AD, investigate the disease's pathogenesis and develop therapies for the disease. Several pharmacological compounds have been developed for AD based on findings from non-human-derived cell models; however, these pharmacological compounds have failed at different phases of clinical trials. This necessitates the application of human-derived cell models, such as induced pluripotent stem cells (iPSCs) in their optimized form in AD mechanistic studies and preclinical drug testing. This review provides an overview of AD and iPSCs. The AD-relevant phenotypes of iPSC-derived AD brain cells and the usefulness of iPSCs in AD are highlighted. Finally, the various recommendations that have been made to enhance iPSC/AD modelling are discussed. LA - English DB - MTMT ER - TY - JOUR AU - Chandrasekaran, Abinaya AU - Jensen, Pia AU - Mohamed, Fadumo A. AU - Lancaster, Madeline AU - Benros, Michael E. AU - Larsen, Martin R. AU - Freude, Kristine K. TI - A protein-centric view of in vitro biological model systems for schizophrenia JF - STEM CELLS J2 - STEM CELLS VL - 39 PY - 2021 IS - 12 SP - 1569 EP - 1578 PG - 10 SN - 1066-5099 DO - 10.1002/stem.3447 UR - https://m2.mtmt.hu/api/publication/32287695 ID - 32287695 N1 - Funding Agency and Grant Number: Innovationsfonden; LundbeckfondenLundbeckfonden Funding text: Innovationsfonden, Grant/Award Numbers: BrainStem, NeuroStem; Lundbeckfonden, Grant/Award Number: Developnoid AB - Schizophrenia (SCZ) is a severe brain disorder, characterized by psychotic, negative, and cognitive symptoms, affecting 1% of the population worldwide. The precise etiology of SCZ is still unknown; however, SCZ has a high heritability, and is associated with genetic, environmental, and social risk factors. Even though the genetic contribution is indisputable, the discrepancies between transcriptomics and proteomics in brain tissues are consistently challenging the field to decipher the disease pathology. Here we provide an overview of the state of the art of neuronal two-dimensional and three-dimensional model systems that can be combined with proteomics analyses to decipher specific brain pathology and detection of alternative entry points for drug development. LA - English DB - MTMT ER - TY - JOUR AU - Chang, Po-Hsiang AU - Chao, Hsiao-Mei AU - Chern, Edward AU - Hsu, Shan-hui TI - Chitosan 3D cell culture system promotes naive-like features of human induced pluripotent stem cells: A novel tool to sustain pluripotency and facilitate differentiation JF - BIOMATERIALS J2 - BIOMATERIALS VL - 268 PY - 2021 SN - 0142-9612 DO - 10.1016/j.biomaterials.2020.120575 UR - https://m2.mtmt.hu/api/publication/31882108 ID - 31882108 N1 - Funding Agency and Grant Number: Program of Regenerative Medicine, Ministry of Science and Technology (MOST), Taiwan [MOST 109-2321-B-002-044, MOST 109-2320-B-002-051-MY2, NSC 100-2314-B-002-002] Funding text: This study was supported by grants from the Program of Regenerative Medicine, Ministry of Science and Technology (MOST), Taiwan (MOST 109-2321-B-002-044, MOST 109-2320-B-002-051-MY2 and NSC 100-2314-B-002-002). We are grateful for Dr. Su-Yi Tsai to assist the procedure of cardiomyocyte differentiation. We also thank the excellent technical support of Technology Commons, College of Life Science, National Taiwan University. AB - A simplified and cost-effective culture system for maintaining the pluripotency of human induced pluripotent stem cells (hiPSCs) is crucial for stem cell applications. Although recombinant protein-based feeder-free hiPSC culture systems have been developed, their manufacturing processes are expensive and complicated, which hinders hiPSC technology progress. Chitosan, a versatile biocompatible polysaccharide, has been reported as a biomaterial for three-dimensional (3D) cell culture system that promotes the physiological activities of mesenchymal stem cells and cancer cells. In the current study, we demonstrated that chitosan membranes sustained proliferation and pluripotency of hiPSCs in long-term culture (up to 365 days). Moreover, using vitronectin as the comparison group, the pluripotency of hiPSCs grown on the membranes was altered into a naive-like state, which, for pluripotent stem cells, is an earlier developmental stage with higher stemness. On the chitosan membranes, hiPSCs self-assembled into 3D spheroids with an average diameter of similar to 100 mu m. These hiPSC spheroids could be directly differentiated into lineage-specific cells from the three germ layers with 3D structures. Collectively, chitosan membranes not only promoted the naive pluripotent features of hiPSCs but also provided a novel 3D differentiation platform. This convenient biomaterial-based culture system may enable the effective expansion and accessibility of hiPSCs for regenerative medicine, disease modeling, and drug screening. LA - English DB - MTMT ER - TY - JOUR AU - ElGindi, Mei AU - Sapudom, Jiranuwat AU - Ibrahim, Ibrahim Hamed AU - Al-Sayegh, Mohamed AU - Chen, Weiqiang AU - Garcia-Sabate, Anna AU - Teo, Jeremy C. M. TI - May the Force Be with You (Or Not): The Immune System under Microgravity JF - CELLS J2 - CELLS-BASEL VL - 10 PY - 2021 IS - 8 PG - 21 SN - 2073-4409 DO - 10.3390/cells10081941 UR - https://m2.mtmt.hu/api/publication/32287692 ID - 32287692 N1 - Funding Agency and Grant Number: New York University Abu Dhabi (NYUAD) Faculty Research Fund [AD266]; NYUAD Research Enhancement Fund [RE267] Funding text: This research was funded by New York University Abu Dhabi (NYUAD) Faculty Research Fund (AD266) and NYUAD Research Enhancement Fund (RE267). AB - All terrestrial organisms have evolved and adapted to thrive under Earth's gravitational force. Due to the increase of crewed space flights in recent years, it is vital to understand how the lack of gravitational forces affects organisms. It is known that astronauts who have been exposed to microgravity suffer from an array of pathological conditions including an impaired immune system, which is one of the most negatively affected by microgravity. However, at the cellular level a gap in knowledge exists, limiting our ability to understand immune impairment in space. This review highlights the most significant work done over the past 10 years detailing the effects of microgravity on cellular aspects of the immune system. LA - English DB - MTMT ER - TY - JOUR AU - Gonmanee, Thanasup AU - Arayapisit, Tawepong AU - Vongsavan, Kutkao AU - Phruksaniyom, Chareerut AU - Sritanaudomchai, Hathaitip TI - Optimal culture conditions for neurosphere formation and neuronal differentiation from human dental pulp stem cells JF - JOURNAL OF APPLIED ORAL SCIENCE J2 - J APPL ORAL SCI VL - 29 PY - 2021 PG - 11 SN - 1678-7757 DO - 10.1590/1678-7757-2021-0296 UR - https://m2.mtmt.hu/api/publication/32468380 ID - 32468380 N1 - Cited By :1 Export Date: 11 October 2022 Correspondence Address: Sritanaudomchai, H.; Mahidol University, Thailand; email: hathaitip.sri@mahidol.ac.th AB - Objectives: Human dental pulp stem cells (DPSCs) have been used to regenerate damaged nervous tissues. However, the methods of committing DPSCs into neural stem/progenitor cells (NSPCs) or neurospheres are highly diverse, resulting in many neuronal differentiation outcomes. This study aims to validate an optimal protocol for inducing DPSCs into neurospheres and neurons. Methodology: After isolation and characterization of mesenchymal stem cell identity, DPSCs were cultured in a NSPC induction medium and culture vessels. The durations of the culture, dissociation methods, and passage numbers of DPSCs were varied. Results: Neurosphere formation requires a special surface that inhibits cell attachment. Five-days was the most appropriate duration for generating proliferative neurospheres and they strongly expressed Nestin, an NSPC marker. Neurosphere reformation after being dissociated by the Accutase enzyme was significantly higher than other methods. Passage number of DPSCs did not affect neurosphere formation, but did influence neuronal differentiation. We found that the cells expressing a neuronal marker, beta-tubulin III, and exhibiting neuronal morphology were significantly higher in the early passage of the DPSCs. Conclusion: These results suggest a guideline to obtain a high efficiency of neurospheres and neuronal differentiation from DPSCs for further study and neurodegeneration therapeutics. LA - English DB - MTMT ER - TY - JOUR AU - Heuer, Rachel A. AU - Nella, Kevin T. AU - Chang, Hsiang-Tsun AU - Coots, Kyle S. AU - Oleksijew, Andrew M. AU - Roque, Christian B. AU - Silva, Luisa H. A. AU - McGuire, Tammy L. AU - Homma, Kazuaki AU - Matsuoka, Akihiro J. TI - Three-Dimensional Otic Neuronal Progenitor Spheroids Derived from Human Embryonic Stem Cells JF - TISSUE ENGINEERING PART A J2 - TISSUE ENG PT A VL - 27 PY - 2021 IS - 3-4 SP - 256 EP - 269 PG - 14 SN - 1937-3341 DO - 10.1089/ten.tea.2020.0078 UR - https://m2.mtmt.hu/api/publication/31467828 ID - 31467828 N1 - Funding Agency and Grant Number: American Otological Society; Triological Society/American College of Surgeons; Department of Otolaryngology, Feinberg School of Medicine, Northwestern University; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [K08DC13829-02]; Office of the Assistant Secretary of Defense of Health Affairs through the Hearing Restoration Research Program [RH170013:WU81XWUH-18-0712] Funding text: This work was supported by the American Otological Society Clinician Scientist Award (A.J.M.), the Triological Society/American College of Surgeons Clinician Scientist Award (A.J.M.), the Department of Otolaryngology, Feinberg School of Medicine, Northwestern University (A.J.M.), NIH K08 Clinician Scientist Award K08DC13829-02 (A.J.M.), and the Office of the Assistant Secretary of Defense of Health Affairs through the Hearing Restoration Research Program (Award #: RH170013:WU81XWUH-18-0712). AB - Stem cell-replacement therapies have been proposed as a potential tool to treat sensorineural hearing loss by aiding the regeneration of spiral ganglion neurons (SGNs) in the inner ear. However, transplantation procedures have yet to be explored thoroughly to ensure proper cell differentiation and optimal transplant procedures. We hypothesized that the aggregation of human embryonic stem cell (hESC)-derived otic neuronal progenitor (ONP) cells into a multicellular form would improve their function and their survivalin vivopost-transplantation. We generated hESC-derived ONP spheroids-an aggregate form conducive to differentiation, transplantation, and prolonged cell survival-to optimize conditions for their transplantation. Our findings indicate that these cell spheroids maintain the molecular and functional characteristics similar to those of ONP cells, which are upstream in the SGN lineage. Moreover, our phenotypical, electrophysiological, and mechanical data suggest an optimal spheroid transplantation point after 7 days ofin vitrothree-dimensional (3D) culture. We have also developed a feasible transplantation protocol for these spheroids using a micropipette aided by a digital microinjection system. In summary, the present work demonstrates that the transplantation of ONP cells in spheroid form into the inner ear through micropipette 7 days after seeding for 3D spheroid culture is an expedient and viable method for stem cell replacement therapies in the inner ear.Impact statement Sensorineural hearing loss affects millions of people worldwide. Although inner ear stem cell replacement therapies offer a promising method to mitigate this hearing loss by aiding in the regeneration of spiral ganglion neurons, fewin vivostudies have been performed in this area. By providing detailed cell spheroid characterization, determining an optimal development stage for transplantation, and establishing a reliable and reproducible transplantation protocol, we aimed to provide the necessary details to bridge the gap betweenin vitroexperiments andin vivostudies of stem cell replacement therapies in the inner ear. LA - English DB - MTMT ER - TY - JOUR AU - Jiang, Hailun AU - Ashraf, Ghulam Md AU - Liu, Mimin AU - Zhao, Kaiyue AU - Wang, Yu AU - Wang, Linlin AU - Xing, Jianguo AU - Alghamdi, Badrah S. AU - Li, Zhuorong AU - Liu, Rui TI - Tilianin Ameliorates Cognitive Dysfunction and Neuronal Damage in Rats with Vascular Dementia via p-CaMKII/ERK/CREB and ox-CaMKII-Dependent MAPK/NF-kappa B Pathways JF - OXIDATIVE MEDICINE AND CELLULAR LONGEVITY J2 - OXID MED CELL LONGEV VL - 2021 PY - 2021 PG - 18 SN - 1942-0900 DO - 10.1155/2021/6673967 UR - https://m2.mtmt.hu/api/publication/32287690 ID - 32287690 N1 - Funding Agency and Grant Number: National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [U1803281, 81673411]; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2018RC350013]; Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science [2017-I2M1-016] Funding text: This work was supported by the National Natural Science Foundation of China (Nos. U1803281 and 81673411), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018RC350013), and the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (2017-I2M1-016). AB - Vascular dementia (VaD) is a common cause of cognitive decline and dementia of vascular origin, but the precise pathological mechanisms are unknown, and so effective clinical treatments have not been established. Tilianin, the principal active compound of total flavonoid extract from Dracocephalum moldavica L., is a candidate therapy for cardio-cerebrovascular diseases in China. However, its potential in the treatment of VaD is unclear. The present study is aimed at investigating the protective effects of tilianin on VaD and exploring the underlying mechanism of the action. A model of VaD was established by permanent 2-vessel occlusion (2VO) in rats. Human neurons (hNCs) differentiated from human-induced pluripotent stem cells were used to establish an oxygen-glucose deprivation (OGD) model. The therapeutic effects and potential mechanisms of tilianin were identified using behavioral tests, histochemistry, and multiple molecular biology techniques such as Western blot analysis and gene silencing. The results demonstrated that tilianin modified spatial cognitive impairment, neurodegeneration, oxidation, and apoptosis in rats with VaD and protected hNCs against OGD by increasing cell viability and decreasing apoptosis rates. A study of the mechanism indicated that tilianin restored p-CaMKII/ERK1/2/CREB signaling in the hippocampus, maintaining hippocampus-independent memory. In addition, tilianin inhibited an ox-CaMKII/p38 MAPK/JNK/NF-kappa B associated inflammatory response caused by cerebral oxidative stress imbalance in rats with VaD. Furthermore, specific CaMKII alpha siRNA action revealed that tilianin-exerted neuroprotection involved increase of neuronal viability, inhibition of apoptosis, and suppression of inflammation, which was dependent on CaMKII alpha. In conclusion, the results suggested the neuroprotective effect of tilianin in VaD and the potential mechanism associated with dysfunction in the regulation of p-CaMKII-mediated long-term memory and oxidation and inflammation involved with ox-CaMKII, which may lay the foundation for clinical trials of tilianin for the treatment of VaD in the future. LA - English DB - MTMT ER - TY - JOUR AU - Mollo, Nunzia AU - Esposito, Matteo AU - Aurilia, Miriam AU - Scognamiglio, Roberta AU - Accarino, Rossella AU - Bonfiglio, Ferdinando AU - Cicatiello, Rita AU - Charalambous, Maria AU - Procaccini, Claudio AU - Micillo, Teresa AU - Genesio, Rita AU - Cali, Gaetano AU - Secondo, Agnese AU - Paladino, Simona AU - Matarese, Giuseppe AU - De Vita, Gabriella AU - Conti, Anna AU - Nitsch, Lucio AU - Izzo, Antonella TI - Human Trisomic iPSCs from Down Syndrome Fibroblasts Manifest Mitochondrial Alterations Early during Neuronal Differentiation JF - BIOLOGY-BASEL J2 - BIOLOGY-BASEL VL - 10 PY - 2021 IS - 7 PG - 24 SN - 2079-7737 DO - 10.3390/biology10070609 UR - https://m2.mtmt.hu/api/publication/32287696 ID - 32287696 N1 - Funding Agency and Grant Number: Jerome Lejeune Foundation Funding text: We acknowledge Jerome Lejeune Foundation for continuous support. We thank Maria Imma Chianese, Flaviana Gentile and Mario Senesi for technical support. AB - Simple Summary Down Syndrome, which is due to the presence of three copies of chromosome 21, always presents with mental retardation, possibly caused by defects in the development of neurons. In recent years, it has been shown that cells and tissues in Down syndrome manifest alterations in the function of mitochondria, the organelles that provide energy to cells. We hypothesized that mitochondrial dysfunction might contribute to the defect in neuronal cell development. To test this hypothesis, we generated a model of stem cells that, upon specific treatments, are capable of giving rise to neuronal cells, as evidenced by the synthesis of specific proteins. We observed that stem cells derived from Down syndrome individuals, after 21 days of growth in an artificial system, had an abnormal tendency to develop as glial cells, compared with control cells. As early as day 7 of culture, the trisomic cells also exhibited defects in mitochondrial function, such as anomalies in their calcium level, oxygen free radicals, oxygen consumption, and synthesis of ATP, a molecule that is critical in energy conversions. These results indicate that alterations in neuronal development and mitochondrial function occur early in this model, which we think is suitable for answering further questions. Background: The presence of mitochondrial alterations in Down syndrome suggests that it might affect neuronal differentiation. We established a model of trisomic iPSCs, differentiating into neural precursor cells (NPCs) to monitor the occurrence of differentiation defects and mitochondrial dysfunction. Methods: Isogenic trisomic and euploid iPSCs were differentiated into NPCs in monolayer cultures using the dual-SMAD inhibition protocol. Expression of pluripotency and neural differentiation genes was assessed by qRT-PCR and immunofluorescence. Meta-analysis of expression data was performed on iPSCs. Mitochondrial Ca2+, reactive oxygen species (ROS) and ATP production were investigated using fluorescent probes. Oxygen consumption rate (OCR) was determined by Seahorse Analyzer. Results: NPCs at day 7 of induction uniformly expressed the differentiation markers PAX6, SOX2 and NESTIN but not the stemness marker OCT4. At day 21, trisomic NPCs expressed higher levels of typical glial differentiation genes. Expression profiles indicated that mitochondrial genes were dysregulated in trisomic iPSCs. Trisomic NPCs showed altered mitochondrial Ca2+, reduced OCR and ATP synthesis, and elevated ROS production. Conclusions: Human trisomic iPSCs can be rapidly and efficiently differentiated into NPC monolayers. The trisomic NPCs obtained exhibit greater glial-like differentiation potential than their euploid counterparts and manifest mitochondrial dysfunction as early as day 7 of neuronal differentiation. LA - English DB - MTMT ER - TY - THES AU - Natalya, Anne Ortolano TI - Identification of CUL9-Related Signaling Pathways in Human Pluripotent Stem Cells and Cortical Precursors PY - 2021 UR - https://m2.mtmt.hu/api/publication/32789450 ID - 32789450 LA - English DB - MTMT ER - TY - JOUR AU - Ortolano, Natalya A. AU - Romero-Morales, Alejandra I AU - Rasmussen, Megan L. AU - Bodnya, Caroline AU - Kline, Leigh A. AU - Joshi, Piyush AU - Connelly, Jon P. AU - Rose, Kristie L. AU - Pruett-Miller, Shondra M. AU - Gama, Vivian TI - A proteomics approach for the identification of cullin-9 (CUL9) related signaling pathways in induced pluripotent stem cell models JF - PLOS ONE J2 - PLOS ONE VL - 16 PY - 2021 IS - 3 PG - 29 SN - 1932-6203 DO - 10.1371/journal.pone.0248000 UR - https://m2.mtmt.hu/api/publication/32287698 ID - 32287698 N1 - Funding Agency and Grant Number: HHS \ NIH \ National Institute of General Medical Sciences (NIGMS) [1R35GM128915-01]; HHS \ National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1R21CA227483-01A1]; HHS \ NIH \ National Institute of Neurological Disorders and Stroke (NINDS) [F31NS10858]; HHS \ NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [5T32HD7502-20] Funding text: HHS vertical bar NIH vertical bar National Institute of General Medical Sciences (NIGMS):Vivian Gama 1R35GM128915-01; HHS vertical bar National Institutes of Health (NIH):Vivian Gama 1R21CA227483-01A1; HHS vertical bar NIH vertical bar National Institute of Neurological Disorders and Stroke (NINDS):Natalya Ortolano F31NS10858; HHS vertical bar NIH vertical bar Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):Natalya Ortolano 5T32HD7502-20 https://www.nih.gov/The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. AB - CUL9 is a non-canonical and poorly characterized member of the largest family of E3 ubiquitin ligases known as the Cullin RING ligases (CRLs). Most CRLs play a critical role in developmental processes, however, the role of CUL9 in neuronal development remains elusive. We determined that deletion or depletion of CUL9 protein causes aberrant formation of neural rosettes, an in vitro model of early neuralization. In this study, we applied mass spectrometric approaches in human pluripotent stem cells (hPSCs) and neural progenitor cells (hNPCs) to identify CUL9 related signaling pathways that may contribute to this phenotype. Through LC-MS/MS analysis of immunoprecipitated endogenous CUL9, we identified several subunits of the APC/C, a major cell cycle regulator, as potential CUL9 interacting proteins. Knockdown of the APC/C adapter protein FZR1 resulted in a significant increase in CUL9 protein levels, however, CUL9 does not appear to affect protein abundance of APC/C subunits and adapters or alter cell cycle progression. Quantitative proteomic analysis of CUL9 KO hPSCs and hNPCs identified protein networks related to metabolic, ubiquitin degradation, and transcriptional regulation pathways that are disrupted by CUL9 deletion in both hPSCs. No significant changes in oxygen consumption rates or ATP production were detected in either cell type. The results of our study build on current evidence that CUL9 may have unique functions in different cell types and that compensatory mechanisms may contribute to the difficulty of identifying CUL9 substrates. LA - English DB - MTMT ER - TY - JOUR AU - Pollard, Kevin J AU - Bolon, Brad AU - Moore, Michael J TI - Comparative Analysis of Chemotherapy-Induced Peripheral Neuropathy in Bioengineered Sensory Nerve Tissue Distinguishes Mechanistic Differences in Early-Stage Vincristine-, Cisplatin-, and Paclitaxel-Induced Nerve Damage JF - TOXICOLOGICAL SCIENCES J2 - TOXICOL SCI VL - 180 PY - 2021 IS - 1 SP - 76 EP - 88 PG - 13 SN - 1096-6080 DO - 10.1093/toxsci/kfaa186 UR - https://m2.mtmt.hu/api/publication/31882241 ID - 31882241 N1 - Funding Agency and Grant Number: United States National Institutes of Health/National Center for Advancing Translational Sciences (NIH/NCATS) [R42-TR001270] Funding text: United States National Institutes of Health/National Center for Advancing Translational Sciences (NIH/NCATS) (Grant No. R42-TR001270). LA - English DB - MTMT ER - TY - JOUR AU - Pollard, Kevin J. AU - Bowser, Devon A. AU - Anderson, Wesley A. AU - Meselhe, Mostafa AU - Moore, Michael J. TI - Morphine-sensitive synaptic transmission emerges in embryonic rat microphysiological model of lower afferent nociceptive signaling JF - SCIENCE ADVANCES J2 - SCI ADV VL - 7 PY - 2021 IS - 35 PG - 18 SN - 2375-2548 DO - 10.1126/sciadv.abj2899 UR - https://m2.mtmt.hu/api/publication/32287694 ID - 32287694 N1 - Funding Agency and Grant Number: NIH National Center for Advancing Translational Sciences [R42-TR001270, UG3-TR003150]; Louisiana Board of Regents Departmental Enhancement Grant [LEQSF (2018-23)-ENH-DE-15] Funding text: This work was funded by grants from the NIH National Center for Advancing Translational Sciences, R42-TR001270 and UG3-TR003150. The Olympus confocal microscope was funded by the Louisiana Board of Regents Departmental Enhancement Grant LEQSF (2018-23)-ENH-DE-15. AB - Debilitating chronic pain resulting from genetic predisposition, injury, or acquired neuropathy is becoming increasingly pervasive. Opioid analgesics remain the gold standard for intractable pain, but overprescription of increasingly powerful and addictive opioids has contributed to the current prescription drug abuse epidemic. There is a pressing need to screen experimental compounds more efficiently for analgesic potential that remains unmet by conventional research models. The spinal cord dorsal horn is a common target for analgesic intervention, where peripheral nociceptive signals are relayed to the central nervous system through synaptic transmission. Here, we demonstrate that coculturing peripheral and dorsal spinal cord nerve cells in a novel bioengineered microphysiological system facilitates self-directed emergence of native nerve tissue macrostructure and concerted synaptic function. The mechanistically distinct analgesics-morphine, lidocaine, and clonidine- differentially and predictably modulate this microphysiological synaptic transmission. Screening drug candidates for similar microphysiological profiles will efficiently identify therapeutics with analgesic potential. LA - English DB - MTMT ER - TY - JOUR AU - Salcedo, Claudia AU - Wagner, Antonie AU - Andersen, Jens V. AU - Vinten, Kasper Tore AU - Waagepetersen, Helle S. AU - Schousboe, Arne AU - Freude, Kristine K. AU - Aldana, Blanca I. TI - Downregulation of GABA Transporter 3 (GAT3) is Associated with Deficient Oxidative GABA Metabolism in Human Induced Pluripotent Stem Cell-Derived Astrocytes in Alzheimer's Disease JF - NEUROCHEMICAL RESEARCH J2 - NEUROCHEM RES VL - 46 PY - 2021 IS - 10 SP - 2676 EP - 2686 PG - 11 SN - 0364-3190 DO - 10.1007/s11064-021-03276-3 UR - https://m2.mtmt.hu/api/publication/32287691 ID - 32287691 N1 - Funding Agency and Grant Number: National Council of Science and Technology (CONACYT)Consejo Nacional de Ciencia y Tecnologia (CONACyT) [2018-000009-01EXTF-00121]; Innovation Fund Denmark "Brainstem" [4108-00008B]; Tommerhandler Vilhelm Bangs Fond; Torben & Alice Frimodts Fond; Ludvig Tegners' Legat; Innovation Fund Denmark "NeuroStem" Funding text: This work was supported by grants from: The National Council of Science and Technology (CONACYT), (grant number 2018-000009-01EXTF-00121 to CS); and Innovation Fund Denmark "Brainstem" (grant number 4108-00008B) and "NeuroStem" (to KKF). [U-13C]GABA was purchased with support from Tommerhandler Vilhelm Bangs Fond, Torben & Alice Frimodts Fond and Ludvig Tegners' Legat (grants to JVA). AB - Alterations in neurotransmitter homeostasis, primarily of glutamate and GABA, is strongly implicated in the pathophysiology of Alzheimer's disease (AD). Homeostasis at the synapse is maintained by neurotransmitter recycling between neurons and astrocytes. Astrocytes support neuronal transmission through glutamine synthesis, which can be derived from oxidative metabolism of GABA. However, the precise implications of astrocytic GABA metabolism in AD remains elusive. The aim of this study was to investigate astrocytic GABA metabolism in AD pathology implementing human induced pluripotent stem cells derived astrocytes. Metabolic mapping of GABA was performed with [U-C-13]GABA stable isotopic labeling using gas chromatography coupled to mass spectrometry (GC-MS). Neurotransmitter and amino acid content was quantified via high performance liquid chromatography (HPLC) and protein expression was investigated by Western blot assay. Cell lines carrying mutations in either amyloid precursor protein (APP) or presenilin1 (PSEN-1) were used as AD models and were compared to a control cell line of the same genetic background. AD astrocytes displayed a reduced oxidative GABA metabolism mediated by a decreased uptake capacity of GABA, as GABA transporter 3 (GAT3) was downregulated in AD astrocytes compared to the controls. Interestingly, the carbon backbone of GABA in AD astrocytes was utilized to a larger extent to support glutamine synthesis compared to control astrocytes. The results strongly indicate alterations in GABA uptake and metabolism in AD astrocytes linked to reduced GABA transporter expression, hereby contributing further to neurotransmitter disturbances. LA - English DB - MTMT ER - TY - JOUR AU - Salcedo, Claudia AU - Andersen, Jens V. AU - Vinten, Kasper Tore AU - Pinborg, Lars H. AU - Waagepetersen, Helle S. AU - Freude, Kristine K. AU - Aldana, Blanca I. TI - Functional Metabolic Mapping Reveals Highly Active Branched-Chain Amino Acid Metabolism in Human Astrocytes, Which Is Impaired in iPSC-Derived Astrocytes in Alzheimer's Disease JF - FRONTIERS IN AGING NEUROSCIENCE J2 - FRONT AGING NEUROSCI VL - 13 PY - 2021 SN - 1663-4365 DO - 10.3389/fnagi.2021.736580 UR - https://m2.mtmt.hu/api/publication/32468477 ID - 32468477 N1 - Funding Agency and Grant Number: National Council of Science and Technology (CONACYT)Consejo Nacional de Ciencia y Tecnologia (CONACyT) Funding text: Funding This study was supported by grants from The National Council of Science and Technology (CONACYT), (PhD Grant No: 2018-000009-01EXTF-00121 to CS), The Scholarship of Peter & Emma Thomsen (to JA), Aase and Ejnar Danielsen Foundation (Grant No: 10-002028 to JA), the Augustinus Foundation (Grant No: 17-4115 to JA), and Innovation Fund Denmark Brainstem (Grant No: 4108-00008B) and NeuroStem (to KF). LA - English DB - MTMT ER - TY - CHAP AU - Taga, A. AU - Maragakis, N.J. TI - Human induced pluripotent stem cell–derived astrocytes progenitors as discovery platforms: opportunities and challenges T2 - iPSC Derived Progenitors PB - Elsevier SN - 9780323900737 T3 - iPSC Derived Progenitors PY - 2021 SP - 45 EP - 89 PG - 45 DO - 10.1016/B978-0-323-85545-7.00005-3 UR - https://m2.mtmt.hu/api/publication/34779263 ID - 34779263 N1 - Export Date: 9 April 2024 LA - English DB - MTMT ER - TY - JOUR AU - Taga, Arens AU - Habela, Christa W. AU - Johns, Alexandra AU - Liu, Shiyu AU - O'Brien, Mollie AU - Maragakis, Nicholas J. TI - Establishment of an Electrophysiological Platform for Modeling ALS with Regionally-Specific Human Pluripotent Stem Cell-Derived Astrocytes and Neurons JF - JOVE-JOURNAL OF VISUALIZED EXPERIMENTS J2 - JOVE-J VIS EXP PY - 2021 IS - 174 PG - 19 SN - 1940-087X DO - 10.3791/62726 UR - https://m2.mtmt.hu/api/publication/32468379 ID - 32468379 N1 - Funding Agency and Grant Number: NIH/NINDSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [K08NS102526]; 2020 Doris Duke Charitable Foundation Clinical Scientist Career Development; DOD ALSRP [W81XWH2010161]; [2019 MSCRFF 5119]; [1R01NS117604-01NIH/NINDS]; [2019 MSCRFD 5122] Funding text: This manuscript was supported by the following: 2019 MSCRFF 5119 (AT). K08NS102526 NIH/NINDS (CWH), 2020 Doris Duke Charitable Foundation Clinical Scientist Career Development Award (CWH). 1R01NS117604-01NIH/NINDS (NJM), DOD ALSRP W81XWH2010161 (NJM), 2019 MSCRFD 5122 (NJM). We thank Dr. Raha Dastgheyb and Dr. Norman Haughey for providing the MEA platform and data analysis software we have utilized to validate the described electrophysiological platform. AB - Human pluripotent stem cell-derived astrocytes (hiPSC-A) and neurons (hiPSCN) provide a powerful tool for modeling Amyotrophic Lateral Sclerosis (ALS) pathophysiology in vitro. Multi-electrode array (MEA) recordings are a means to record electrical field potentials from large populations of neurons and analyze network activity over time. It was previously demonstrated that the presence of hiPSC-A that are differentiated using techniques to promote a spinal cord astrocyte phenotype improved maturation and electrophysiological activity of regionally specific spinal cord hiPSC-motor neurons (MN) when compared to those cultured without hiPSCA or in the presence of rodent astrocytes. Described here is a method to co-culture spinal cord hiPSC-A with hiPSC-MN and record electrophysiological activity using MEA recordings. While the differentiation protocols described here are particular to astrocytes and neurons that are regionally specific to the spinal cord, the co-culturing platform can be applied to astrocytes and neurons differentiated with techniques specific to other fates, including cortical hiPSC-A and hiPSC-N. These protocols aim to provide an electrophysiological assay to inform about glia-neuron interactions and provide a platform for testing drugs with therapeutic potential in ALS. LA - English DB - MTMT ER - TY - JOUR AU - Wang, Dimin AU - Wang, Kai AU - Liu, Zhenlei AU - Wang, Zonglin AU - Wu, Hao TI - Valproic Acid Labeled Chitosan Nanoparticles Promote the Proliferation and Differentiation of Neural Stem Cells After Spinal Cord Injury JF - NEUROTOXICITY RESEARCH J2 - NEUROTOX RES VL - 39 PY - 2021 SP - 456 EP - 466 PG - 11 SN - 1029-8428 DO - 10.1007/s12640-020-00304-y UR - https://m2.mtmt.hu/api/publication/31882110 ID - 31882110 N1 - Funding Agency and Grant Number: Natural Science Foundation of Beijing (NSF) [KZ201910025028] Funding text: This work was supported by Natural Science Foundation of Beijing (NSF) grant (KZ201910025028). AB - Chitosan nanoparticles and valproic acid are demonstrated as the protective agents in the treatment of spinal cord injury (SCI). However, the effects of valproic acid-labeled chitosan nanoparticles (VA-CN) on endogenous spinal cord neural stem cells (NSCs) following SCI and the underlying mechanisms involved remain to be elucidated. In this study, the VA-CN was constructed and the effects of VA-CN on NSCs were assessed in a rat model of SCI. We found VA-CN treatment promoted recovery of the tissue and locomotive function following SCI. Moreover, administration of VA-CN significantly enhanced neural stem cell proliferation and the expression levels of neurotrophic factors following SCI. Furthermore, administration of VA-CN led to a decrease in the number of microglia following SCI. In addition, VA-CN treatment significantly increased the Tuj 1- positive cells in the spinal cord of the SCI rats, suggesting that VA-CN could enhance the differentiation of NSCs following SCI. In conclusion, these results demonstrated that VA-CN could improve the functional and histological recovery through promoting the proliferation and differentiation of NSCs following SCI, which would provide a newly potential therapeutic manner for the treatment of SCI. LA - English DB - MTMT ER - TY - JOUR AU - Abdullah, Mohammed A. A. AU - Amini, Nooshin AU - Yang, Liwei AU - Paluh, Janet L. AU - Wang, Jun TI - Multiplexed analysis of neural cytokine signaling by a novel neural cell-cell interaction microchip JF - LAB ON A CHIP J2 - LAB CHIP VL - 20 PY - 2020 IS - 21 SP - 3980 EP - 3995 PG - 16 SN - 1473-0197 DO - 10.1039/d0lc00401d UR - https://m2.mtmt.hu/api/publication/31685840 ID - 31685840 N1 - Funding Agency and Grant Number: New York State Stem Cell Science [C32574GG]; National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01GM12898401] Funding text: This research is supported by the New York State Stem Cell Science (C32574GG) to JW and JLP, and the National Institute of Health (R01GM12898401) to JW. AB - Multipotent neural stem cells (NSCs) are widely applied in pre-clinical and clinical trials as a cell source to promote tissue regeneration in neurodegenerative diseases. Frequently delivered as dissociated cells, aggregates or self-organized rosettes, it is unknown whether disruption of the NSC rosette morphology or method of formation affect signaling profiles of these cells that may impact uniformity of outcomes in cell therapies. Here we generate a neural cell-cell interaction microchip (NCCIM) as an in vitro platform to simultaneously track an informed panel of cytokines and co-evaluate cell morphology and biomarker expression coupled to a sandwich ELISA platform. We apply multiplex in situ tagging technology (MIST) to evaluate ten cytokines (PDGF-AA, GDNF, BDNF, IGF-1, FGF-2, IL-6, BMP-4, CNTF, beta-NGF, NT-3) on microchips for EB-derived rosettes, single cell dissociated rosettes and reformed rosette neurospheres. Of the cytokines evaluated, EB-derived rosettes secrete PDGF-AA, GDNF and FGF-2 prominently, whereas this profile is temporarily lost upon dissociation to single cells and in reformed neurospheres two additional cytokines, BDNF and beta-NGF, are also secreted. This study on NSC rosettes demonstrates the development, versatility and utility of the NCCIM as a sensitive multiplex detector of cytokine signaling in a high throughput and controlled microenvironment. The NCCIM is expected to provide important new information to refine cell source choices in therapies as well as to support development of informative 2D or 3D in vitro models including areas of neurodegeneration or neuroplasticity. LA - English DB - MTMT ER - TY - THES AU - Alastair, Grainger TI - Development of human induced pluripotent stem cell-derived neural cultures for seizure-liability testing PY - 2020 UR - https://m2.mtmt.hu/api/publication/32468444 ID - 32468444 LA - English DB - MTMT ER - TY - JOUR AU - Alsanie, Walaa F. AU - Bahri, Ola A. AU - Habeeballah, Hamza H. AU - Alhomrani, Majid AU - Almehmadi, Mazen M. AU - Alsharif, Khalaf AU - Felemban, Ebaa M. AU - Althobaiti, Yusuf S. AU - Almalki, Atiah H. AU - Alsaab, Hashem O. AU - Gaber, Ahmed AU - Hassan, Mohamed M. AU - Hardy, Ana Maria Gregio AU - Alhadidi, Qasim TI - Generating homogenous cortical preplate and deep-layer neurons using a combination of 2D and 3D differentiation cultures JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 10 PY - 2020 IS - 1 SN - 2045-2322 DO - 10.1038/s41598-020-62925-9 UR - https://m2.mtmt.hu/api/publication/31391465 ID - 31391465 N1 - Funding Agency and Grant Number: Ministry of Education post-doctoral fellowships (Saudi Arabia); [1-438-5988] Funding text: The authors would like to thank the deanship of scientific research for their financial support for this project (project no. 1-438-5988). H.H. and O. B. are supported by the Ministry of Education post-doctoral fellowships (Saudi Arabia). LA - English DB - MTMT ER - TY - JOUR AU - Chang, Hsiang-Tsun AU - Heuer, Rachel A. AU - Oleksijew, Andrew M. AU - Coots, Kyle S. AU - Roque, Christian B. AU - Nella, Kevin T. AU - McGuire, Tammy L. AU - Matsuoka, Akihiro J. TI - An engineered three-dimensional stem cell niche in the inner ear by applying a nanofibrillar cellulose hydrogel with a sustained-release neurotrophic factor delivery system JF - ACTA BIOMATERIALIA J2 - ACTA BIOMATER VL - 108 PY - 2020 SP - 111 EP - 127 PG - 17 SN - 1742-7061 DO - 10.1016/j.actbio.2020.03.007 UR - https://m2.mtmt.hu/api/publication/31467830 ID - 31467830 N1 - Funding Agency and Grant Number: American Otological Society Clinician Scientist Award; Triological Society/American College of Surgeons Clinician Scientist Award; Department of Otolaryngology of Northwestern University; NIH (NIDCD) K08 Clinician Scientist Award [K08DC13829-02]; Office of the Assistant Secretary of Defense of Health Affairs through the Hearing Restoration Research Program [RH170013:WU81XWUH-18-0712]; NCI CCSG [P30 CA060553]; Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource [NSFECCS-1542205] Funding text: This work was supported by the American Otological Society Clinician Scientist Award (AJM), the Triological Society/American College of Surgeons Clinician Scientist Award (AJM), the Department of Otolaryngology of Northwestern University (AJM), the NIH (NIDCD) K08 Clinician Scientist Award K08DC13829-02 (AJM), and the Office of the Assistant Secretary of Defense of Health Affairs through the Hearing Restoration Research Program (Award #: RH170013:WU81XWUH-18-0712). Imaging work was performed at the Northwestern University Center for Advanced Microscopy, which is generously supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center, for which we thank Peter Dluhy, Constadina Arvanitis, Ph.D., David Kirchenbuechler, Ph.D., and Wensheng (Wilson) Liu, M.D. Our rheological and viscoelastic experiments were performed in the Analytical bioNanoTechnology (ANTEC) Core Facility of the Simpson Querrey Institute at Northwestern University, which is supported by the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSFECCS-1542205. We thank Duncan Chadly (Caltech) and Shun Kobayashi (The Uiverstiy of Texas at Austin) for their contribution to the earlier phases of this project. We thank Jason Luo (Optic11 Life), Alexandra Kolot (ANTEC), Charles Bressan (ANTEC) for assistance in the use of a Piuma nadoindenter and Tony Kiuru, Markus Nuopponen, Ph.D., Lauri Paasonen, Ph.D. (UPM), Jonathan Sheard, Ph.D. (Sheard Biotech, Ltd.), and Christian Pernstich, Ph.D. (Cell Guidance System) for insightful comments and proofreading this manuscript. Flow Cytometry data were acquired with the assistance from Robert H. Lurie Comprehensive Cancer Center -Flow Cytometry Core Facility, for which we thank Suchitra Swaminathan, Ph.D and Carolina Ostiguin. AB - Although the application of human embryonic stem cells (hESCs) in stem cell-replacement therapy remains promising, its potential is hindered by a low cell survival rate in post-transplantation within the inner ear. Here, we aim to enhance the in vitro and in vivo survival rate and neuronal differentiation of otic neuronal progenitors (ONPs) by generating an artificial stem cell niche consisting of three-dimensional (3D) hESC-derived ONP spheroids with a nanofibrillar cellulose hydrogel and a sustained-release brainderivative neurotrophic factor delivery system. Our results demonstrated that the transplanted hESC-derived ONP spheroids survived and neuronally differentiated into otic neuronal lineages in vitro and in vivo and also extended neurites toward the bony wall of the cochlea 90 days after the transplantation without the use of immunosuppressant medication. Our data in vitro and in vivo presented here provide sufficient evidence that we have established a robust, reproducible protocol for in vivo transplantation of hESC-derived ONPs to the inner ear. Using our protocol to create an artificial stem cell niche in the inner ear, it is now possible to work on integrating transplanted hESC-derived ONPs further and also to work toward achieving functional auditory neurons generated from hESCs. Our findings suggest that the provision of an artificial stem cell niche can be a future approach to stem cell-replacement therapy for inner-ear regeneration.Statement of SignificanceInner ear regeneration utilizing human embryonic stem cell-derived otic neuronal progenitors (hESC-derived ONPs) has remarkable potential for treating sensorineural hearing loss. However, the local environment of the inner ear requires a suitable stem cell niche to allow hESC-derived ONP engraftment as well as neuronal differentiation. To overcome this obstacle, we utilized three-dimensional spheroid formation (direct contact), nanofibrillar cellulose hydrogel (extracellular matrix), and a neurotrophic factor delivery system to artificially create a stem cell niche in vitro and in vivo. Our in vitro and in vivo data presented here provide sufficient evidence that we have established a robust, reproducible protocol for in vivo transplantation of hESC-derived ONPs to the inner ear. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Chlebanowska, Paula AU - Sulkowski, Maciej AU - Skrzypek, Klaudia AU - Tejchman, Anna AU - Muszynska, Agata AU - Noroozi, Rezvan AU - Majka, Marcin TI - Origin of the Induced Pluripotent Stem Cells Affects Their Differentiation into Dopaminergic Neurons JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 21 PY - 2020 IS - 16 PG - 23 SN - 1661-6596 DO - 10.3390/ijms21165705 UR - https://m2.mtmt.hu/api/publication/31685837 ID - 31685837 N1 - Funding Agency and Grant Number: National Science Centre in PolandNational Science Centre, Poland [2015/17/B/NZ5/00294]; Jagiellonian University Medical College [K/ZDS/007055, N41/DBS/000132, K/DSC/005287, N41/DBS/000120] Funding text: This research was funded by the National Science Centre in Poland grant no. 2015/17/B/NZ5/00294 and from Jagiellonian University Medical College grant no. K/ZDS/007055, N41/DBS/000132, K/DSC/005287 and N41/DBS/000120. AB - Neuronal differentiation of human induced pluripotent stem (iPS) cells, both in 2D models and 3D systems in vitro, allows for the study of disease pathomechanisms and the development of novel therapies. To verify if the origin of donor cells used for reprogramming to iPS cells can influence the differentiation abilities of iPS cells, peripheral blood mononuclear cells (PBMC) and keratinocytes were reprogrammed to iPS cells using the Sendai viral vector and were subsequently checked for pluripotency markers and the ability to form teratomas in vivo. Then, iPS cells were differentiated into dopaminergic neurons in 2D and 3D cultures. Both PBMC and keratinocyte-derived iPS cells were similarly reprogrammed to iPS cells, but they displayed differences in gene expression profiles and in teratoma compositions in vivo. During 3D organoid formation, the origin of iPS cells affected the levels of FOXA2 and LMX1A only in the first stages of neural differentiation, whereas in the 2D model, differences were detected at the levels of both early and late neural markers FOXA2, LMX1A, NURR1, TUBB and TH. To conclude, the origin of iPS cells may significantly affect iPS differentiation abilities in teratomas, as well as exerting effects on 2D differentiation into dopaminergic neurons and the early stages of 3D midbrain organoid formation. LA - English DB - MTMT ER - TY - JOUR AU - de Leeuw, Victoria C. AU - van Oostrom, Conny T. M. AU - Imholz, Sandra AU - Piersma, Aldert H. AU - Hessel, Ellen V. S. AU - Dolle, Martijn E. T. TI - Going Back and Forth: Episomal Vector Reprogramming of Peripheral Blood Mononuclear Cells to Induced Pluripotent Stem Cells and Subsequent Differentiation into Cardiomyocytes and Neuron-Astrocyte Co-cultures JF - CELLULAR REPROGRAMMING J2 - CELL REPROGRAM VL - 22 PY - 2020 IS - 6 SP - 300 EP - 310 PG - 11 SN - 2152-4971 DO - 10.1089/cell.2020.0040 UR - https://m2.mtmt.hu/api/publication/31685844 ID - 31685844 N1 - Funding Agency and Grant Number: National Institute of Health (NIH)/National Institute of Aging (NIA)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [AG017242]; Dutch Ministry of Agriculture, Nature and Food Quality; Dutch Ministry of Health, Welfare and Sports; Dutch NGO Stichting Proefdiervrij Funding text: This research is funded by the National Institute of Health (NIH)/National Institute of Aging (NIA) (AG017242), the Dutch Ministry of Agriculture, Nature and Food Quality, the Dutch Ministry of Health, Welfare and Sports, and the Dutch NGO Stichting Proefdiervrij. AB - Human induced pluripotent stem cells (iPSCs) can capture the diversity in the general human population as well as provide deeper insight in cellular mechanisms. This makes them suitable to study both fundamental and applied research subjects, such as disease modeling, gene-environment interactions, personalized medicine, and chemical toxicity. In an independent laboratory, we were able to generate iPSCs originating from human peripheral blood mononuclear cells according to a modified version of a temporal episomal vector (EV)-based induction method. The iPSCs could subsequently be differentiated into two different lineages: mesoderm-derived cardiomyocytes and ectoderm-derived neuron-astrocyte co-cultures. It was shown that the neuron-astrocyte culture developed a mature phenotype within the course of five weeks and depending on the medium composition, network formation and neuron-astrocyte cell ratios could be modified. Although previously it has been described that iPSCs generated with this EV-based induction protocol could differentiate to mesenchymal stem cells, hepatocytes, cardiomyocytes, and basic neuronal cultures, we now demonstrate differentiation into a culture containing both neurons and astrocytes. LA - English DB - MTMT ER - TY - JOUR AU - de, Leeuw Victoria C. AU - van, Oostrom T. M. AU - Westerink, Remco H. S. AU - Piersma, Aldert H. AU - Heusinkveld, Harm J. AU - Hessel, Ellen V. S. TI - An efficient neuron-astrocyte differentiation protocol from human embryonic stem cell-derived neural progenitors to assess chemical-induced developmental neurotoxicity JF - REPRODUCTIVE TOXICOLOGY J2 - REPROD TOXICOL VL - 98 PY - 2020 SP - 107 EP - 116 PG - 10 SN - 0890-6238 DO - 10.1016/j.reprotox.2020.09.003 UR - https://m2.mtmt.hu/api/publication/31882109 ID - 31882109 N1 - Funding Agency and Grant Number: Dutch NGO Stichting Proefdiervrij; Dutch Ministry of Agriculture, Nature and Food Quality; Dutch Ministry of Health, Welfare and Sports Funding text: This research is funded by the Dutch NGO Stichting Proefdiervrij and the Dutch Ministry of Agriculture, Nature and Food Quality and the Dutch Ministry of Health, Welfare and Sports. We would like to thank Fiona Wijnolts, Anke Tukker and the rest of the Neurotoxicology team at IRAS (University Utrecht) for recording the MEA plates. We would like to thank Anne Kienhuis for a critical review of the manuscript. AB - Human embryonic stem cell neuronal differentiation models provide promising in vitro tools for the prediction of developmental neurotoxicity of chemicals. Such models mimic essential elements of human relevant neuronal development, including the differentiation of a variety of brain cell types and their neuronal network formation as evidenced by specific gene and protein biomarkers. However, the reproducibility and lengthy culture duration of cell models present drawbacks and delay regulatory implementation. Here we present a relatively short and robust protocol to differentiate H9-derived neural progenitor cells (NPCs) into a neuron-astrocyte co-culture. When frozen-stored NPCs were re-cultured and induced into neuron-astrocyte differentiation, they showed gene and protein expression typical for these cells, and most notably they exhibited spontaneous electrical activity within three days of culture as measured by a multi-well micro-electrode array. Modulating the ratio of astrocytes and neurons through different growth factors including glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF) did not compromise the ability to develop spontaneous electrical activity. This robust neuronal differentiation model may serve as a functional component of a testing strategy for unravelling mechanisms of developmental neurotoxicity. LA - English DB - MTMT ER - TY - JOUR AU - Galiakberova, Adelya A. AU - Dashinimaev, Erdem B. TI - Neural Stem Cells and Methods for Their Generation From Induced Pluripotent Stem Cellsin vitro JF - FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY J2 - FRONT CELL DEV BIOL VL - 8 PY - 2020 PG - 20 SN - 2296-634X DO - 10.3389/fcell.2020.00815 UR - https://m2.mtmt.hu/api/publication/31685843 ID - 31685843 N1 - Funding Agency and Grant Number: Ministry of Science and Higher Education of the Russian Federation [075-15-2019-1789]; IDB RAS government program of basic research [0108-2019-0004] Funding text: This publication was supported by grant no. 075-15-2019-1789 from the Ministry of Science and Higher Education of the Russian Federation, allocated to the Center for Precision Genome Editing and Genetic Technologies for Biomedicine. The work of ED was supported by the IDB RAS government program of basic research no. 0108-2019-0004. AB - Neural stem cells (NSCs) provide promising approaches for investigating embryonic neurogenesis, modeling of the pathogenesis of diseases of the central nervous system, and for designing drug-screening systems. Such cells also have an application in regenerative medicine. The most convenient and acceptable source of NSCs is pluripotent stem cells (embryonic stem cells or induced pluripotent stem cells). However, there are many different protocols for the induction and differentiation of NSCs, and these result in a wide range of neural cell types. This review is intended to summarize the knowledge accumulated, to date, by workers in this field. It should be particularly useful for researchers who are beginning investigations in this area of cell biology. LA - English DB - MTMT ER - TY - JOUR AU - Guo, Ning-Ning AU - Liu, Li-Ping AU - Zheng, Yun-Wen AU - Li, Yu-Mei TI - Inducing human induced pluripotent stem cell differentiation through embryoid bodies: A practical and stable approach JF - WORLD JOURNAL OF STEM CELLS J2 - WORLD J STEM CELLS VL - 12 PY - 2020 IS - 1 SP - 25 EP - 34 PG - 10 SN - 1948-0210 DO - 10.4252/wjsc.v12.i1.25 UR - https://m2.mtmt.hu/api/publication/31467829 ID - 31467829 N1 - Funding Agency and Grant Number: National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81770621, 81573053]; Ministry of Education, Culture, Sports, Science, and Technology of Japan, KAKENHIMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceGrants-in-Aid for Scientific Research (KAKENHI) [16K15604, 18H02866]; Natural Science Foundation of Jiangsu ProvinceNatural Science Foundation of Jiangsu Province [BK20180281] Funding text: Supported by National Natural Science Foundation of China, No. 81770621, No. 81573053; Ministry of Education, Culture, Sports, Science, and Technology of Japan, KAKENHI, No. 16K15604, No. 18H02866; Natural Science Foundation of Jiangsu Province, No. BK20180281. AB - Human induced pluripotent stem cells (hiPSCs) are invaluable resources for producing high-quality differentiated cells in unlimited quantities for both basic research and clinical use. They are particularly useful for studying human disease mechanisms in vitro by making it possible to circumvent the ethical issues of human embryonic stem cell research. However, significant limitations exist when using conventional flat culturing methods especially concerning cell expansion, differentiation efficiency, stability maintenance and multicellular 3D structure establishment, differentiation prediction. Embryoid bodies (EBs), the multicellular aggregates spontaneously generated from iPSCs in the suspension system, might help to address these issues. Due to the unique microenvironment and cell communication in EB structure that a 2D culture system cannot achieve, EBs have been widely applied in hiPSC-derived differentiation and show significant advantages especially in scaling up culturing, differentiation efficiency enhancement, ex vivo simulation, and organoid establishment. EBs can potentially also be used in early prediction of iPSC differentiation capability. To improve the stability and feasibility of EB-mediated differentiation and generate high quality EBs, critical factors including iPSC pluripotency maintenance, generation of uniform morphology using micro-pattern 3D culture systems, proper cellular density inoculation, and EB size control are discussed on the basis of both published data and our own laboratory experiences. Collectively, the production of a large quantity of homogeneous EBs with high quality is important for the stability and feasibility of many PSCs related studies. LA - English DB - MTMT ER - TY - THES AU - JUSTINE, MARIE NGO TI - Understanding Dishevelled-Mediated Wnt Signaling in Regulating Early Development and Stem Cell Differentiation PY - 2020 UR - https://m2.mtmt.hu/api/publication/32468426 ID - 32468426 LA - English DB - MTMT ER - TY - JOUR AU - Kathuria, Annie AU - Lopez-Lengowski, Kara AU - Watmuff, Bradley AU - Karmacharya, Rakesh TI - Comparative Transcriptomic Analysis of Cerebral Organoids and Cortical Neuron Cultures Derived from Human Induced Pluripotent Stem Cells JF - STEM CELLS AND DEVELOPMENT J2 - STEM CELLS DEV VL - 29 PY - 2020 IS - 21 SP - 1370 EP - 1381 PG - 12 SN - 1547-3287 DO - 10.1089/scd.2020.0069 UR - https://m2.mtmt.hu/api/publication/31685839 ID - 31685839 N1 - Funding Agency and Grant Number: National Institute of Mental Health Biobehavioral Research Awards for Innovative New Scientists (BRAINS) Award [R01MH113858]; Doris Duke Charitable Foundation Clinical Scientist Development AwardAmerican Heart AssociationDoris Duke Charitable Foundation (DDCF) [K08MH086846]; Ryan Licht Sang Bipolar Foundation; Jeanne Marie Lee-Osterhaus Family Foundation NARSAD Young Investigator Award from the Brain & Behavior Research Foundation; Phyllis & Jerome Lyle Rappaport Foundation; Harvard Stem Cell Institute; National Institute of Mental Health Clinical Scientist Development Award [K08MH086846] Funding text: This work was supported by a National Institute of Mental Health Biobehavioral Research Awards for Innovative New Scientists (BRAINS) Award R01MH113858 (to R.K.), National Institute of Mental Health Clinical Scientist Development Award K08MH086846 (to R.K.), the Doris Duke Charitable Foundation Clinical Scientist Development Award (to R.K.), the Ryan Licht Sang Bipolar Foundation (to R.K.), the Jeanne Marie Lee-Osterhaus Family Foundation NARSAD Young Investigator Award from the Brain & Behavior Research Foundation (to A.K.), the Phyllis & Jerome Lyle Rappaport Foundation (to R.K.), the Harvard Stem Cell Institute (to R.K.), and by Steve Willis and Elissa Freud (to R.K.). AB - Human induced pluripotent stem cells (iPSCs) can be differentiated along various neuronal lineages to generate two-dimensional neuronal cultures as well as three-dimensional brain organoids. Such iPSC-derived cellular models are being utilized to study the basic biology of human neuronal function and to interrogate the molecular underpinnings of disease biology. The different cellular models generated from iPSCs have varying properties in terms of the diversity and organization of the cells as well as the cellular functions that are present. To understand transcriptomic differences in iPSC-derived monolayer neuronal cultures and three-dimensional brain organoids, we differentiated eight human iPSC lines from healthy control subjects to generate cerebral organoids and cortical neuron monolayer cultures from the same set of iPSC lines. We undertook RNA-seq experiments in these model systems and analyzed the gene expression data to identify genes that are differentially expressed in cerebral organoids and two-dimensional cortical neuron cultures. In cerebral organoids, gene ontology analysis showed enrichment of genes involved in tissue development, response to stimuli, and the interferon-gamma pathway, while two-dimensional cortical neuron cultures showed enrichment of genes involved in nervous system development and neurogenesis. We also undertook comparative analysis of these gene expression profiles with transcriptomic data from the human fetal prefrontal cortex (PFC). This analysis showed greater overlap of the fetal PFC transcriptome with cerebral organoid gene expression profiles compared to monolayer cortical neuron culture profiles. Our studies delineate the transcriptomic differences between cortical neuron monolayer cultures and three-dimensional cerebral organoids and can help inform the appropriate use of these model systems to address specific scientific questions. LA - English DB - MTMT ER - TY - JOUR AU - Kobolák, Julianna AU - Teglasi, Annamaria AU - Bellák, Tamás AU - Janstova, Zofia AU - Molnár, Kinga AU - Zana, Melinda AU - Bock, Istvan AU - László, Lajos AU - Dinnyés, András TI - Human Induced Pluripotent Stem Cell-Derived 3D-Neurospheres are Suitable for Neurotoxicity Screening JF - CELLS J2 - CELLS-BASEL VL - 9 PY - 2020 IS - 5 PG - 28 SN - 2073-4409 DO - 10.3390/cells9051122 UR - https://m2.mtmt.hu/api/publication/31307709 ID - 31307709 N1 - Funding Agency and Grant Number: European Union's Horizon 2020 research and innovation programme [681002] Funding text: This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 681002 (EU-ToxRisk). AB - We present a hiPSC-based 3D in vitro system suitable to test neurotoxicity (NT). Human iPSCs-derived 3D neurospheres grown in 96-well plate format were characterized timewise for 6-weeks. Changes in complexity and homogeneity were followed by immunocytochemistry and transmission electron microscopy. Transcriptional activity of major developmental, structural, and cell-type-specific markers was investigated at weekly intervals to present the differentiation of neurons, astrocytes, and oligodendrocytes. Neurospheres were exposed to different well-known toxicants with or without neurotoxic effect (e.g., paraquat, acrylamide, or ibuprofen) and examined at various stages of the differentiation with an ATP-based cell viability assay optimized for 3D-tissues. Concentration responses were investigated after acute (72 h) exposure. Moreover, the compound-specific effect of rotenone was investigated by a panel of ER-stress assay, TUNEL assay, immunocytochemistry, electron microscopy, and in 3D-spheroid based neurite outgrowth assay. The acute exposure to different classes of toxicants revealed distinct susceptibility profiles in a differentiation stage-dependent manner, indicating that hiPSC-based 3D in vitro neurosphere models could be used effectively to evaluate NT, and can be developed further to detect developmental neurotoxicity (DNT) and thus replace or complement the use of animal models in various basic research and pharmaceutical applications. LA - English DB - MTMT ER - TY - JOUR AU - Niu, W. AU - Parent, J.M. TI - Modeling genetic epilepsies in a dish JF - DEVELOPMENTAL DYNAMICS J2 - DEV DYNAM VL - 249 PY - 2020 IS - 1 SP - 56 EP - 75 PG - 20 SN - 1058-8388 DO - 10.1002/dvdy.79 UR - https://m2.mtmt.hu/api/publication/31031658 ID - 31031658 N1 - Cited By :19 Export Date: 11 October 2022 CODEN: DEDYE Correspondence Address: Parent, J.M.; Department of Neurology and Neuroscience Graduate Program, United States; email: parent@umich.edu LA - English DB - MTMT ER - TY - JOUR AU - Porterfield, Veronica TI - Neural Progenitor Cell Derivation Methodologies for Drug Discovery Applications JF - ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES J2 - ASSAY DRUG DEV TECHN VL - 18 PY - 2020 IS - 2 SP - 89 EP - 95 PG - 7 SN - 1540-658X DO - 10.1089/adt.2019.921 UR - https://m2.mtmt.hu/api/publication/30712136 ID - 30712136 N1 - Funding Agency and Grant Number: School of Medicine at the University of Virginia Funding text: This article (generation of Fig. 1) was supported by the Stem Cell Core Facilities and the School of Medicine at the University of Virginia. The author appreciates the assistance of Dr. Elizabeth Sharlow in the assembly of this article. AB - Inducible pluripotent stem cells (iPSCs) are being used to model brain disorders across the continuum of neurodevelopment, neurodegenerative, and neuropsychiatric disease allowing for the mechanistic unraveling of the neurological disease state. Subsequently, there is a diverse array of cell model systems that can be used for target validation, pharmacodynamic endpoint development, and high-throughput/content assay development and screening. However, to successfully model neurological disorders with iPSCs, the disease-relevant neuron must be first identified, and it is critical to have the appropriate neuronal progenitor cell derivation and neuron differentiation protocols available to produce desired neuronal phenotypes. Moreover, special considerations are necessary if adaptation to high-throughput/content assay systems is anticipated. Discussed here are the three-dimensional embryoid body-neural rosette and two-dimensional monolayer methodologies to derive iPS neural progenitor cells and neurons with a specific focus on cortical neurons. Outlined are some of the commonalities, advantages, and disadvantages associated with both methodologies. LA - English DB - MTMT ER - TY - JOUR AU - Sharma, Ruchi AU - Smits, Imke P. M. AU - De La Vega, Laura AU - Lee, Christopher AU - Willerth, Stephanie M. TI - 3D Bioprinting Pluripotent Stem Cell Derived Neural Tissues Using a Novel Fibrin Bioink Containing Drug Releasing Microspheres JF - FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY J2 - FRONT BIOENG BIOTECHNOL VL - 8 PY - 2020 PG - 12 SN - 2296-4185 DO - 10.3389/fbioe.2020.00057 UR - https://m2.mtmt.hu/api/publication/31467831 ID - 31467831 N1 - Funding Agency and Grant Number: NSERCNatural Sciences and Engineering Research Council of Canada (NSERC); Innovate BC's Ignite Program; Alzheimer's AssociationAlzheimer's Association; Michael Smith Foundation for Health ResearchMichael Smith Foundation for Health Research; Pacific Parkinson's Research Institute; Canada Research Chairs ProgramCanada Research Chairs Funding text: This work was funded by the NSERC Discovery Grant Program, NSERC Idea to Innovation Program, Innovate BC's Ignite Program, the Alzheimer's Association, and the Michael Smith Foundation for Health Research and Pacific Parkinson's Research Institute's Innovation to Commercialization Grant. This work was also funded by the Canada Research Chairs Program. AB - 3D bioprinting combines cells with a supportive bioink to fabricate multiscale, multi-cellular structures that imitate native tissues. Here, we demonstrate how our novel fibrin-based bioink formulation combined with drug releasing microspheres can serve as a tool for bioprinting tissues using human induced pluripotent stem cell (hiPSC)-derived neural progenitor cells (NPCs). Microspheres, small spherical particles that generate controlled drug release, promote hiPSC differentiation into dopaminergic neurons when used to deliver small molecules like guggulsterone. We used the microfluidics based RX1 bioprinter to generate domes with a 1 cm diameter consisting of our novel fibrin-based bioink containing guggulsterone microspheres and hiPSC-derived NPCs. The resulting tissues exhibited over 90% cellular viability 1 day post printing that then increased to 95% 7 days post printing. The bioprinted tissues expressed the early neuronal marker, TUJ1 and the early midbrain marker, Forkhead Box A2 (FOXA2) after 15 days of culture. These bioprinted neural tissues expressed TUJ1 (15 +/- 1.3%), the dopamine marker, tyrosine hydroxylase (TH) (8 +/- 1%) and other glial markers such as glial fibrillary acidic protein (GFAP) (15 +/- 4%) and oligodendrocyte progenitor marker (O4) (4 +/- 1%) after 30 days. Also, quantitative polymerase chain reaction (qPCR) analysis showed these bioprinted tissues expressed TUJ1, NURR1 (gene expressed in midbrain dopaminergic neurons), LMX1B, TH, and PAX6 after 30 days. In conclusion, we have demonstrated that using a microsphere-laden bioink to bioprint hiPSC-derived NPCs can promote the differentiation of neural tissue. LA - English DB - MTMT ER - TY - JOUR AU - Alia, Claudia AU - Terrigno, Marco AU - Busti, Irene AU - Cremisi, Federico AU - Caleo, Matteo TI - Pluripotent Stem Cells for Brain Repair: Protocols and Preclinical Applications in Cortical and Hippocampal Pathologies JF - FRONTIERS IN NEUROSCIENCE J2 - FRONT NEUROSCI-SWITZ VL - 13 PY - 2019 PG - 15 SN - 1662-4548 DO - 10.3389/fnins.2019.00684 UR - https://m2.mtmt.hu/api/publication/30782994 ID - 30782994 N1 - CNR Neuroscience Institute, National Research Council (CNR), Pisa, Italy Laboratory of Biology, Scuola Normale Superiore, Pisa, Italy Department of Neuroscience, Psychology, Drugs and Child Health Area, School of Psychology, University of Florence, Florence, Italy Biophysics Institute (IBF), National Research Council (CNR), Pisa, Italy Department of Biomedical Sciences, University of Padua, Padua, Italy Padua Neuroscience Center, University of Padua, Padua, Italy Cited By :1 Export Date: 30 May 2020 Correspondence Address: Alia, C.; CNR Neuroscience Institute, National Research Council (CNR)Italy; email: alia@in.cnr.it Funding details: Horizon 2020 Framework Programme, H2020 Funding details: European Research Council, ERC, 692943 Funding details: Accademia Nazionale dei Lincei Funding text 1: CA was supported by a fellowship from the Accademia Nazionale dei Lincei. This work was supported by the H2020 EXCELLENT SCIENCE – European Research Council (ERC) under grant agreement ID no. 692943 (BrainBIT). CNR Neuroscience Institute, National Research Council (CNR), Pisa, Italy Laboratory of Biology, Scuola Normale Superiore, Pisa, Italy Department of Neuroscience, Psychology, Drugs and Child Health Area, School of Psychology, University of Florence, Florence, Italy Biophysics Institute (IBF), National Research Council (CNR), Pisa, Italy Department of Biomedical Sciences, University of Padua, Padua, Italy Padua Neuroscience Center, University of Padua, Padua, Italy Cited By :4 Export Date: 6 May 2021 Correspondence Address: Alia, C.; CNR Neuroscience Institute, Italy; email: alia@in.cnr.it Funding details: Horizon 2020 Framework Programme, H2020 Funding details: European Research Council, ERC, 692943 Funding details: Accademia Nazionale dei Lincei Funding text 1: CA was supported by a fellowship from the Accademia Nazionale dei Lincei. This work was supported by the H2020 EXCELLENT SCIENCE – European Research Council (ERC) under grant agreement ID no. 692943 (BrainBIT). AB - Brain injuries causing chronic sensory or motor deficit, such as stroke, are among the leading causes of disability worldwide, according to the World Health Organization; furthermore, they carry heavy social and economic burdens due to decreased quality of life and need of assistance. Given the limited effectiveness of rehabilitation, novel therapeutic strategies are required to enhance functional recovery. Since cell-based approaches have emerged as an intriguing and promising strategy to promote brain repair, many efforts have been made to study the functional integration of neurons derived from pluripotent stem cells (PSCs), or fetal neurons, after grafting into the damaged host tissue. PSCs hold great promises for their clinical applications, such as cellular replacement of damaged neural tissues with autologous neurons. They also offer the possibility to create in vitro models to assess the efficacy of drugs and therapies. Notwithstanding these potential applications, PSC-derived transplanted neurons have to match the precise sub-type, positional and functional identity of the lesioned neural tissue. Thus, the requirement of highly specific and efficient differentiation protocols of PSCs in neurons with appropriate neural identity constitutes the main challenge limiting the clinical use of stem cells in the near future. In this Review, we discuss the recent advances in the derivation of telencephalic (cortical and hippocampal) neurons from PSCs, assessing specificity and efficiency of the differentiation protocols, with particular emphasis on the genetic and molecular characterization of PSC-derived neurons. Second, we address the remaining challenges for cellular replacement therapies in cortical brain injuries, focusing on electrophysiological properties, functional integration and therapeutic effects of the transplanted neurons. LA - English DB - MTMT ER - TY - JOUR AU - Antill-O'Brien, Natasha AU - Bourke, Justin AU - O'Connell, Cathal D. TI - Layer-By-Layer: The Case for 3D Bioprinting Neurons to Create Patient-Specific Epilepsy Models JF - MATERIALS J2 - MATERIALS VL - 12 PY - 2019 IS - 19 PG - 42 SN - 1996-1944 DO - 10.3390/ma12193218 UR - https://m2.mtmt.hu/api/publication/30997152 ID - 30997152 N1 - Funding Agency and Grant Number: St Vincent's Research Endowment Fund [88306] Funding text: This research was funded by St Vincent's Research Endowment Fund, grant number 88306. AB - The ability to create three-dimensional (3D) models of brain tissue from patient-derived cells, would open new possibilities in studying the neuropathology of disorders such as epilepsy and schizophrenia. While organoid culture has provided impressive examples of patient-specific models, the generation of organised 3D structures remains a challenge. 3D bioprinting is a rapidly developing technology where living cells, encapsulated in suitable bioink matrices, are printed to form 3D structures. 3D bioprinting may provide the capability to organise neuronal populations in 3D, through layer-by-layer deposition, and thereby recapitulate the complexity of neural tissue. However, printing neuron cells raises particular challenges since the biomaterial environment must be of appropriate softness to allow for the neurite extension, properties which are anathema to building self-supporting 3D structures. Here, we review the topic of 3D bioprinting of neurons, including critical discussions of hardware and bio-ink formulation requirements. LA - English DB - MTMT ER - TY - JOUR AU - Bell, Scott AU - Hettige, Nuwan C. AU - Silveira, Heika AU - Peng, Huashan AU - Wu, Hanrong AU - Jefri, Malvin AU - Antonyan, Lilit AU - Zhang, Ying AU - Zhang, Xin AU - Ernst, Carl TI - Differentiation of Human Induced Pluripotent Stem Cells (iPSCs) into an Effective Model of Forebrain Neural Progenitor Cells and Mature Neurons JF - BIO-PROTOCOL J2 - BIO-PROTOCOL VL - 9 PY - 2019 IS - 5 SN - 2331-8325 DO - 10.21769/BioProtoc.3188 UR - https://m2.mtmt.hu/api/publication/30712137 ID - 30712137 N1 - Funding Agency and Grant Number: Canada Research Chairs programCanada Research Chairs; Canadian Institute of Health ResearchCanadian Institutes of Health Research (CIHR); (Fonds de la recherche en sante du Quebec) FRQS; FRQS; Government of Malaysia; CONACYT (Mexico)Consejo Nacional de Ciencia y Tecnologia (CONACyT) Funding text: This work was supported by grants from the Canada Research Chairs program and the Canadian Institute of Health Research to CE. Scott Bell is funded by the (Fonds de la recherche en sante du Quebec) FRQS, Nuwan Hettige is funded by FRQS, Malvin Jefri is supported by the Government of Malaysia, and Lilit Antonyan is supported by CONACYT (Mexico). This protocol was adapted from previous work (Bell et al., 2017 and 2018). AB - Induced Pluripotent Stem Cells (iPSCs) are pluripotent stem cells that can be generated from somatic cells, and provide a way to model the development of neural tissues in vitro. One particularly interesting application of iPSCs is the development of neurons analogous to those found in the human forebrain. Forebrain neurons play a central role in cognition and sensory processing, and deficits in forebrain neuronal activity contributes to a host of conditions, including epilepsy, Alzheimer's disease, and schizophrenia. Here, we present our protocol for differentiating iPSCs into forebrain neural progenitor cells (NPCs) and neurons, whereby neural rosettes are generated from stem cells without dissociation and NPCs purified from rosettes based on their adhesion, resulting in a more rapid generation of pure NPC cultures. Neural progenitor cells can be maintained as long-term cultures, or differentiated into forebrain neurons. This protocol provides a simplified and fast methodology of generating forebrain NPCs and neurons, and enables researchers to generate effective in vitro models to study forebrain disease and neurodevelopment. This protocol can also be easily adapted to generate other neural lineages. LA - English DB - MTMT ER - TY - THES AU - Biró, Orsolya TI - A mikroRNS-ek patogenetikai szerepe és expressziós mintázata praeeclampsiában PY - 2019 DO - 10.14753/SE.2019.2269 UR - https://m2.mtmt.hu/api/publication/30859380 ID - 30859380 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Csobonyeiova, Maria AU - Polak, Stefan AU - Zamborsky, Radoslav AU - Danisovic, Lubos TI - Recent Progress in the Regeneration of Spinal Cord Injuries by Induced Pluripotent Stem Cells JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 20 PY - 2019 IS - 15 PG - 13 SN - 1661-6596 DO - 10.3390/ijms20153838 UR - https://m2.mtmt.hu/api/publication/30997153 ID - 30997153 N1 - Funding Agency and Grant Number: Slovak Research and Development AgencySlovak Research and Development Agency [APVV-14-0032] Funding text: This research was funded by Slovak Research and Development Agency, grant number APVV-14-0032. AB - Regeneration of injuries occurring in the central nervous system, particularly spinal cord injuries (SCIs), is extremely difficult. The complex pathological events following a SCI often restrict regeneration of nervous tissue at the injury site and frequently lead to irreversible loss of motor and sensory function. Neural stem/progenitor cells (NSCs/NPCs) possess neuroregenerative and neuroprotective features, and transplantation of such cells into the site of damaged tissue is a promising stem cell-based therapy for SCI. However, NSC/NPCs have mostly been induced from embryonic stem cells or fetal tissue, leading to ethical concerns. The pioneering work of Yamanaka and colleagues gave rise to the technology to induce pluripotent stem cells (iPSCs) from somatic cells, overcoming these ethical issues. The advent of iPSCs technology has meant significant progress in the therapy of neurodegenerative disease and nerve tissue damage. A number of published studies have described the successful differentiation of NSCs/NPCs from iPSCs and their subsequent engraftment into SCI animal models, followed by functional recovery of injury. The aim of this present review is to summarize various iPSC- NPCs differentiation methods, SCI modelling, and the current status of possible iPSC- NPCs- based therapy of SCI. LA - English DB - MTMT ER - TY - JOUR AU - Gopalakrishnan, Jay TI - The Emergence of Stem Cell-Based Brain Organoids: Trends and Challenges JF - BIOESSAYS J2 - BIOESSAYS VL - 41 PY - 2019 IS - 8 PG - 10 SN - 0265-9247 DO - 10.1002/bies.201900011 UR - https://m2.mtmt.hu/api/publication/30782998 ID - 30782998 N1 - Institut für Humangenetik, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. 1, Düsseldorf, 40225, Germany IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, 40225, Germany Cited By :21 Export Date: 11 October 2022 CODEN: BIOEE Correspondence Address: Gopalakrishnan, J.; Institut für Humangenetik, Universitätsstr. 1, Germany; email: jay.gopalakrishnan@hhu.de AB - Recent developments in 3D cultures exploiting the self-organization ability of pluripotent stem cells have enabled the generation of powerful in vitro systems termed brain organoids. These 3D tissues recapitulate many aspects of human brain development and disorders occurring in vivo. When combined with improved differentiation methods, these in vitro systems allow the generation of more complex "assembloids," which are able to reveal cell diversities, microcircuits, and cell-cell interactions within their 3D organization. Here, the ways in which human brain organoids have contributed to demystifying the complexities of brain development and modeling of developmental disorders is reviewed and discussed. Furthermore, challenging questions that are yet to be addressed by emerging brain organoid research are discussed. LA - English DB - MTMT ER - TY - JOUR AU - Han, Hao-Wei AU - Asano, Shigetaka AU - Hsu, Shan-hui TI - Cellular Spheroids of Mesenchymal Stem Cells and Their Perspectives in Future Healthcare JF - APPLIED SCIENCES-BASEL J2 - APPL SCI-BASEL VL - 9 PY - 2019 IS - 4 SN - 2076-3417 DO - 10.3390/app9040627 UR - https://m2.mtmt.hu/api/publication/30712138 ID - 30712138 N1 - Funding Agency and Grant Number: Program for Regenerative Medicine [MOST 107-2321-B-002-040]; National Taiwan UniversityNational Taiwan University [NTU-107L4000]; National Health Research Institutes (Central Government S T Grant) [107-0324-01-19-03] Funding text: This work was supported by the Program for Regenerative Medicine (MOST 107-2321-B-002-040), funding of National Taiwan University for the postdoctoral fellowship (NTU-107L4000), and funding of National Health Research Institutes (Central Government S & T Grant 107-0324-01-19-03). AB - Intrinsic cellular properties of several types of cells are dramatically altered as the culture condition shifts from two-dimensional (2D) to three-dimensional (3D) environment. Currently, several lines of evidence have demonstrated the therapeutic potential of mesenchymal stem cells (MSCs) in regenerative medicine. MSCs not only replenish the lost cells, they also promote the regeneration of impaired tissues by modulating the immune responses. Following the development of 3D cell culture, the enhanced therapeutic efficacy of spheroid-forming MSCs have been identified in several animal disease models by promoting differentiation or trophic factor secretion, as compared to planar-cultured MSCs. Due to the complicated and multifunctional applications in the medical field, MSCs are recently named as medicinal signaling cells. In this review, we summarize the predominant differences of cell-environment interactions for the MSC spheroids formed by chitosan-based substrates and other scaffold-free approaches. Furthermore, several important physical and chemical factors affecting cell behaviors in the cell spheroids are discussed. Currently, the understanding of MSCs spheroid interactions is continuously expanding. Overall, this article aims to review the broad advantages and perspectives of MSC spheroids in regenerative medicine and in future healthcare. LA - English DB - MTMT ER - TY - JOUR AU - Harknes, Linda AU - Chen, Xiaoli AU - Jia, Zhongfan AU - Davies, Anthony M. AU - Monteiro, Michael AU - Gray, Peter AU - Pera, Martin TI - Fibronectin-conjugated thermoresponsive nanobridges generate three dimensional human pluripotent stem cell cultures for differentiation towards the neural lineages JF - STEM CELL RESEARCH J2 - STEM CELL RES VL - 38 PY - 2019 PG - 11 SN - 1873-5061 DO - 10.1016/j.scr.2019.101441 UR - https://m2.mtmt.hu/api/publication/30782995 ID - 30782995 N1 - Funding Agency and Grant Number: Stem Cells Australia; Australian Research Council Strategic Initiative in Stem Cell ScienceAustralian Research Council [SR110001002]; JEM Research Foundation; Merchant Charitable Foundation; University of QueenslandUniversity of Queensland Funding text: The authors would like to acknowledge funding from Stem Cells Australia, an Australian Research Council Strategic Initiative in Stem Cell Science (SR110001002), the JEM Research Foundation philanthropic funding, The Merchant Charitable Foundation and the University of Queensland for their support and funding of this work. This work was performed in part at the Queensland node of the Australian National Fabrication Facility. A company established under the National Collaborative Research Infrastructure Strategy to provide nano and microfabrication facilities for Australia's researchers. The authors declare no conflict of interest. AB - Production of 3-dimensional neural progenitor cultures from human pluripotent stem cells offers the potential to generate large numbers of cells. We utilised our nanobridge system to generate 3D hPSC aggregates for differentiation towards the neural lineage, and investigate the ability to passage aggregates while maintaining cells at a stem/progenitor stage. Over 38 days, aggregate cultures exhibited upregulation and maintenance of neural-associated markers and demonstrated up to 10 fold increase in cell number. Aggregates undergoing neural induction in the presence or absence of nanobridges demonstrated no differences in marker expression, proliferation or viability. However, aggregates formed without nanobridges were statistically significantly fewer and smaller by passage 3. Organoids, cultured from aggregates, and treated with retinoic acid or rock inhibitor demonstrated terminal differentiation as assessed by immunohistochemistry. These data demonstrate that nanobridge 3D hPSC can differentiate to neural stem/progenitor cells, and be maintained at this stage through serial passaging and expansion. LA - English DB - MTMT ER - TY - JOUR AU - Kim, Jaemin AU - Nonis, David AU - Gabriela Otero, Maria AU - Mark Pierson, Tyler TI - Modeling rare pediatric neurogenetic disorders with IPSCs JF - AIMS Cell and Tissue Engineering J2 - AIMS Cell and Tissue Engineering VL - 3 PY - 2019 IS - 1 SP - 1 EP - 25 PG - 25 SN - 2574-0105 DO - 10.3934/celltissue.2019.1.1 UR - https://m2.mtmt.hu/api/publication/30670996 ID - 30670996 LA - English DB - MTMT ER - TY - CHAP AU - Kuusisto, Finn AU - Santos Costa, Vitor AU - Hou, Zhonggang AU - Thomson, James AU - Page, David AU - Stewart, Ron ED - Arif Wani, M. ED - M. Khoshgoftaar, Taghi ED - Wang, Dingding ED - Wang, Huanjing ED - (Jim) Seliya, Naeem TI - Machine Learning to Predict Developmental Neurotoxicity with High-Throughput Data from 2D Bio-Engineered Tissues T2 - 2019 18th IEEE International Conference On Machine Learning And Applications (ICMLA) PB - IEEE Computer Society CY - Washington DC SN - 9781728145501 PY - 2019 SP - 293 EP - 298 PG - 6 DO - 10.1109/ICMLA.2019.00055 UR - https://m2.mtmt.hu/api/publication/31882251 ID - 31882251 N1 - Cited By :2 Export Date: 11 October 2022 Correspondence Address: Kuusisto, F.; Morgridge Institute for Research, United States; email: fkuusisto@morgridge.org LA - English DB - MTMT ER - TY - THES AU - Laura, De la Vega Reyes TI - Novel Techniques for Engineering Neural Tissue Using Human Induced Pluripotent Stem Cells PY - 2019 UR - https://m2.mtmt.hu/api/publication/32468456 ID - 32468456 LA - English DB - MTMT ER - TY - JOUR AU - Ojeda, Jorge AU - Avila, Ariel TI - Early Actions of Neurotransmitters During Cortex Development and Maturation of Reprogrammed Neurons JF - FRONTIERS IN SYNAPTIC NEUROSCIENCE J2 - FRONT SYNAPTIC NEURO VL - 11 PY - 2019 PG - 14 SN - 1663-3563 DO - 10.3389/fnsyn.2019.00033 UR - https://m2.mtmt.hu/api/publication/30997151 ID - 30997151 N1 - Funding Agency and Grant Number: "Vicerrectoria de Investigacion y Postgrados (VRIP)'' of the Universidad Catolica de la Santisima Concepcion; Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)+PAI+ CONVOCATORIA NACIONAL SUBVENCION A INSTALACION EN LA ACADEMIA CONVOCATORIA ANO 2018 +Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) [PAI77180086] Funding text: JO is funded by internal funds of the "Vicerrectoria de Investigacion y Postgrados (VRIP)'' of the Universidad Catolica de la Santisima Concepcion. AA is funded by Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)+PAI+ CONVOCATORIA NACIONAL SUBVENCION A INSTALACION EN LA ACADEMIA CONVOCATORIA ANO 2018 + Grant number: PAI77180086. AB - The development of the brain is shaped by a myriad of factors among which neurotransmitters play remarkable roles before and during the formation and maturation of synaptic circuits. Cellular processes such as neurogenesis, morphological development, synaptogenesis and maturation of synapses are temporary and spatially regulated by the local or distal influence of neurotransmitters in the developing cortex. Thus, research on this area has contributed to the understanding of fundamental mechanisms of brain development and to shed light on the etiology of various human neurodevelopmental disorders such as autism and Rett syndrome (RTT), among others. Recently, the field of neuroscience has been shaken by an explosive advance of experimental approaches linked to the use of induced pluripotent stem cells and reprogrammed neurons. This new technology has allowed researchers for the first time to model in the lab the unique events that take place during early human brain development and to explore the mechanisms that cause synaptopathies. In this context, the role of neurotransmitters during early stages of cortex development is beginning to be re-evaluated and a revision of the state of the art has become necessary in a time when new protocols are being worked out to differentiate stem cells into functional neurons. New perspectives on reconsidering the function of neurotransmitters include opportunities for methodological advances, a better understanding of the origin of mental disorders and the potential for development of new treatments. LA - English DB - MTMT ER - TY - JOUR AU - Peng, Chunyang AU - Li, Yajiao AU - Lu, Li AU - Zhu, Jianwen AU - Li, Huiyu AU - Hu, Jingqiong TI - Efficient One-Step Induction of Human Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSCs) Produces MSC-Derived Neurospheres (MSC-NS) with Unique Transcriptional Profile and Enhanced Neurogenic and Angiogenic Secretomes JF - STEM CELLS INTERNATIONAL J2 - STEM CELLS INT VL - 2019 PY - 2019 PG - 15 SN - 1687-966X DO - 10.1155/2019/9208173 UR - https://m2.mtmt.hu/api/publication/31573030 ID - 31573030 N1 - Emergency Internal Medicine Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China Stem Cell Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China Department of Oncology, Xiangfan Central Hospital, Xiangfan, Hubei, China Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China Department of Gynaecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China Cited By :22 Export Date: 9 April 2024 Correspondence Address: Hu, J.; Stem Cell Center, China; email: jingqionghu2006@sina.com AB - Cell therapy has emerged as a promising strategy for treating neurological diseases such as stroke, spinal cord injury, and various neurodegenerative diseases, but both embryonic neural stem cells and human induced Pluripotent Stem Cell- (iPSC-) derived neural stem cells have major limitations which restrict their broad use in these diseases. We want to find a one-step induction method to transdifferentiate the more easily accessible Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSCs) into neural stem/progenitor cells suitable for cell therapy purposes. In this study, UC-MSCs were induced to form neurospheres under a serum-free suspension culture with Epidermal Growth Factor- (EGF-) and basic Fibroblast Growth Factor- (bFGF-) containing medium within 12 hours. These MSC-derived neurospheres can self-renew to form secondary neurospheres and can be readily induced to become neurons and glial cells. Real-time PCR showed significantly upregulated expression of multiple stemness and neurogenic genes after induction. RNA transcriptional profiling study showed that UC-MSC-derived neurospheres had a unique transcriptional profile of their own, with features of both UC-MSCs and neural stem cells. RayBio human growth factor cytokine array analysis showed significantly upregulated expression levels of multiple neurogenic and angiogenic growth factors, skewing toward a neural stem cell phenotype. Thus, we believe that these UC-MSC-derived neurospheres have amenable features of both MSCs and neural stem/progenitor cells and have great potential in future stem cell transplantation clinical trials targeting neurological disorders. LA - English DB - MTMT ER - TY - JOUR AU - Pollard, Kevin J AU - Sharma, Anup D AU - Moore, Michael J TI - Neural microphysiological systems for in vitro modeling of peripheral nervous system disorders JF - Bioelectronics in Medicine J2 - Bioelectronics in Medicine VL - 2 PY - 2019 IS - 2 SP - 101 EP - 117 PG - 17 SN - 2059-1500 DO - 10.2217/bem-2019-0018 UR - https://m2.mtmt.hu/api/publication/31882187 ID - 31882187 LA - English DB - MTMT ER - TY - JOUR AU - Shen, Xuting AU - Yeung, Hoi Ting AU - Lai, Kwok-On TI - Application of Human-Induced Pluripotent Stem Cells (hiPSCs) to Study Synaptopathy of Neurodevelopmental Disorders JF - DEVELOPMENTAL NEUROBIOLOGY J2 - DEV NEUROBIOL VL - 79 PY - 2019 IS - 1 SP - 20 EP - 35 PG - 16 SN - 1932-8451 DO - 10.1002/dneu.22644 UR - https://m2.mtmt.hu/api/publication/30595646 ID - 30595646 N1 - Funding Agency and Grant Number: Area of Excellence Scheme of the University Grants Committee of Hong Kong [AoE/M-604/16]; Research Grant Council Hong KongHong Kong Research Grants Council [GRF16100814, ECS 27119715, GRF 17135816]; Liu Po Shan/Dr. Vincent Liu Endowment Fund for Motor Neurone Disease Funding text: Contract grant sponsor: The Area of Excellence Scheme of the University Grants Committee of Hong Kong; contract grant AoE/M-604/16.; Contract grant sponsor: Research Grant Council Hong Kong; contract grant GRF16100814, ECS 27119715, GRF 17135816.; Contract grant sponsor: Liu Po Shan/Dr. Vincent Liu Endowment Fund for Motor Neurone Disease AB - Synapses are the basic structural and functional units for information processing and storage in the brain. Their diverse properties and functions ultimately underlie the complexity of human behavior. Proper development and maintenance of synapses are essential for normal functioning of the nervous system. Disruption in synaptogenesis and the consequent alteration in synaptic function have been strongly implicated to cause neurodevelopmental disorders such as autism spectrum disorders (ASDs) and schizophrenia (SCZ). The introduction of human-induced pluripotent stem cells (hiPSCs) provides a new path to elucidate disease mechanisms and potential therapies. In this review, we will discuss the advantages and limitations of using hiPSC-derived neurons to study synaptic disorders. Many mutations in genes encoding for proteins that regulate synaptogenesis have been identified in patients with ASDs and SCZ. We use Methyl-CpG binding protein 2 (MECP2), SH3 and multiple ankyrin repeat domains 3 (SHANK3) and Disrupted in schizophrenia 1 (DISC1) as examples to illustrate the promise of using hiPSCs as cellular models to elucidate the mechanisms underlying disease-related synaptopathy. (c) 2018 Wiley Periodicals, Inc. LA - English DB - MTMT ER - TY - JOUR AU - Yu, Chao AU - Xia, Kaishun AU - Gong, Zhe AU - Ying, Liwei AU - Shu, Jiawei AU - Zhang, Feng AU - Chen, Qixin AU - Li, Fangcai AU - Liang, Chengzhen TI - The Application of Neural Stem/ Progenitor Cells for Regenerative Therapy of Spinal Cord Injury JF - CURRENT STEM CELL RESEARCH AND THERAPY J2 - CURR STEM CELL RES THER VL - 14 PY - 2019 IS - 6 SP - 495 EP - 503 PG - 9 SN - 1574-888X DO - 10.2174/1574888X14666190329095638 UR - https://m2.mtmt.hu/api/publication/30782996 ID - 30782996 N1 - Funding Agency and Grant Number: National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81572177, 81401822, 81472504]; Science and Technology Foundation [2016C33151]; Nature Science Foundation of Zhejiang ProvinceNatural Science Foundation of Zhejiang Province [LGF19H060014, 2018KY092]; health foundation of Zhejiang Province, China [2016146428] Funding text: This study was supported by grants from the National Natural Science Foundation of China (NO. 81572177, NO. 81401822 and NO. 81472504), the Science and Technology Foundation (2016C33151), the Nature Science Foundation (LGF19H060014, 2018KY092) of Zhejiang Province and the health foundation (2016146428) of Zhejiang Province, China. AB - Spinal cord injury (SCI) is a devastating event, and there are still no effective therapies currently available. Neural stem cells (NSCs) have gained increasing attention as promising regenerative therapy of SCI. NSCs based therapies of various neural diseases in animal models and clinical trials have been widely investigated. In this review we aim to summarize the development and recent progress in the application of NSCs in cell transplantation therapy for SCI. After brief introduction on sequential genetic steps regulating spinal cord development in vivo, we describe current experimental approaches for neural induction of NSCs in vitro. In particular, we focus on NSCs induced from pluripotent stem cells (PSCs). Finally, we highlight recent progress on the NSCs, which show great promise in the application to regeneration therapy for SCI. LA - English DB - MTMT ER - TY - JOUR AU - Biró, Orsolya AU - Rigó, János TI - A mikro-RNS-ek patogenetikai szerepe és expressziós mintázata praeeclampsiában JF - ORVOSI HETILAP J2 - ORV HETIL VL - 159 PY - 2018 IS - 14 SP - 547 EP - 556 PG - 10 SN - 0030-6002 DO - 10.1556/650.2018.31025 UR - https://m2.mtmt.hu/api/publication/3357249 ID - 3357249 AB - Preeclampsia is the leading cause of maternal and fetal morbidity and mortality that affects 3-8% of pregnancies worldwide. Its main symptoms include new onset of high blood pressure and proteinuria after 20 weeks of pregnancy. The cause of the disease is still debated. microRNAs are short, non-coding RNA molecules that play a pivotal part in the posttranscriptional regulation of eukaryotic genes. They are involved in fine-tuning of vital physiological processes such as cell cycle, proliferation, differentiation and cell death. In genomic studies, hundreds of microRNAs were detected in the placenta, which are supposed to regulate placental development and contribute to uncomplicated pregnancy. Several studies have reported changes in the expression of microRNAs in pregnancy. Abnormal microRNA expression may have a role in the development of preeclampsia as it affects the proliferation, migration, and invasion of the trophoblast cells, spiral artery remodeling, and angiogenesis. Some placental microRNAs (e.g., the C19MC microRNA cluster) are able to reach the maternal circulation through their release via exosomes from the trophoblast layer. These 'circulating' microRNA molecules can be applied as biomarkers for the detection of various placental disorders owing to their stability and specificity. Orv Hetil. 2018; 159(14): 547-556. LA - Hungarian DB - MTMT ER - TY - THES AU - Geetika, Sahni TI - Micropatterned Neuroectoderm Tissue Model to Study Early Neural Development and Pathogenesis PY - 2018 UR - https://m2.mtmt.hu/api/publication/32789457 ID - 32789457 LA - English DB - MTMT ER - TY - JOUR AU - J Siney, Elodie AU - Kurbatskaya, Ksenia AU - Chatterjee, Shreyasi AU - Prasannan, Preeti AU - Mudher, Amrit AU - Willaime-Morawek, Sandrine TI - Modelling neurodegenerative diseases in vitro: Recent advances in 3D iPSC technologies JF - AIMS Cell and Tissue Engineering J2 - AIMS Cell and Tissue Engineering VL - 2 PY - 2018 IS - 1 SP - 1 EP - 23 PG - 23 SN - 2574-0105 DO - 10.3934/celltissue.2018.1.1 UR - https://m2.mtmt.hu/api/publication/30670991 ID - 30670991 LA - English DB - MTMT ER - TY - JOUR AU - Li, Zhuosi AU - Kurosawa, Osamu AU - Iwata, Hiroo TI - Development of trophoblast cystic structures from human induced pluripotent stem cells in limited-area cell culture JF - BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS J2 - BIOCHEM BIOPH RES CO VL - 505 PY - 2018 IS - 3 SP - 671 EP - 676 PG - 6 SN - 0006-291X DO - 10.1016/j.bbrc.2018.09.181 UR - https://m2.mtmt.hu/api/publication/30598458 ID - 30598458 N1 - Funding Agency and Grant Number: Japan Society for the Promotion of Science (JSPS) (KAKENHI)Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceGrants-in-Aid for Scientific Research (KAKENHI) [18K12071]; "Compass to Healthy Life" Research Complex Program of Japan Science and Technology Agency (JST) Funding text: We thank Professor Washizu of Tokyo University (Tokyo, Japan) and Professor Okeyo of Kyoto University (Kyoto, Japan) for valuable discussions and suggestions. This research was supported by grants from the Japan Society for the Promotion of Science USPS) (KAKENHI Grant Numbers: 18K12071), and the "Compass to Healthy Life" Research Complex Program of Japan Science and Technology Agency (JST). AB - We developed a novel engineering technique to induce differentiation of human induced pluripotent stem cells (hiPSCs) into organoids mimicking the trophectoderm (TE). Here, hiPSCs were cultured on a limited area of 2-4 mm in diameter. After 15-20 days, spherical cysts appeared on the surface of the limited area. Secretion of human chorionic gonadotrophin (hCG) began to increase after -20 days and remained dramatically elevated over the next 20 days. Limited-area-cultured cysts exhibited expression of hCG, which was a result of epithelial differentiation. Low expression levels of pluripotent genes and high expression levels of trophoblast lineage-specific genes were detected in the cells of spherical cysts. Multinucleated syncytia trophoblast was observed in the reseeded cystic cells. We observed hiPSC-derived cysts that morphologically resembled trophectoderm in vivo. The limited-area cell culture induced a three-dimensional (3D) trophectoderm organoid, which has potential for use in the study of human trophoblast differentiation and placental morphogenesis. (C) 2018 Elsevier Inc. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Rosati, Jessica AU - Ferrari, Daniela AU - Altieri, Filomena AU - Tardivo, Silvia AU - Ricciolini, Claudia AU - Fusilli, Caterina AU - Zalfa, Cristina AU - Profico, Daniela C. AU - Pinos, Francesca AU - Bernardini, Laura AU - Torres, Barbara AU - Manni, Isabella AU - Piaggio, Giulia AU - Binda, Elena AU - Copetti, Massimiliano AU - Lamorte, Giuseppe AU - Mazza, Tommaso AU - Carella, Massimo AU - Gelati, Maurizio AU - Valente, Enza Maria AU - Simeone, Antonio AU - Vescovi, Angelo L. TI - Establishment of stable iPS-derived human neural stem cell lines suitable for cell therapies JF - CELL DEATH AND DISEASE J2 - CELL DEATH DIS VL - 9 PY - 2018 PG - 16 SN - 2041-4889 DO - 10.1038/s41419-018-0990-2 UR - https://m2.mtmt.hu/api/publication/30598176 ID - 30598176 N1 - Funding Agency and Grant Number: Italian Ministry of Health, Ricerca Corrente 2014-2017; ERC Starting GrantEuropean Research Council (ERC) [260888]; Association Revert Onlus, Fondazione Cellule Staminali Funding text: This work was supported by Italian Ministry of Health, Ricerca Corrente 2014-2017 to A.L.V.; ERC Starting Grant 260888 to E.M.V., Association Revert Onlus, Fondazione Cellule Staminali. AB - Establishing specific cell lineages from human induced pluripotent stem cells (hiPSCs) is vital for cell therapy approaches in regenerative medicine, particularly for neurodegenerative disorders. While neural precursors have been induced from hiPSCs, the establishment of hiPSC-derived human neural stem cells (hiNSCs), with characteristics that match foetal hNSCs and abide by cGMP standards, thus allowing clinical applications, has not been described. We generated hiNSCs by a virus-free technique, whose properties recapitulate those of the clinical-grade hNSCs successfully used in an Amyotrophic Lateral Sclerosis (ALS) phase I clinical trial. Ex vivo, hiNSCs critically depend on exogenous mitogens for stable self-renewal and amplification and spontaneously differentiate into astrocytes, oligodendrocytes and neurons upon their removal. In the brain of immunodeficient mice, hiNSCs engraft and differentiate into neurons and glia, without tumour formation. These findings now warrant the establishment of clinical-grade, autologous and continuous hiNSC lines for clinical trials in neurological diseases such as Huntington's, Parkinson's and Alzheimer's, among others. LA - English DB - MTMT ER - TY - JOUR AU - Zhang, Meixiang AU - Ngo, Justine AU - Pirozzi, Filomena AU - Sun, Ying-Pu AU - Wynshaw-Boris, Anthony TI - Highly efficient methods to obtain homogeneous dorsal neural progenitor cells from human and mouse embryonic stem cells and induced pluripotent stem cells JF - STEM CELL RESEARCH & THERAPY J2 - STEM CELL RES THER VL - 9 PY - 2018 PG - 13 SN - 1757-6512 DO - 10.1186/s13287-018-0812-6 UR - https://m2.mtmt.hu/api/publication/30997154 ID - 30997154 N1 - Funding Agency and Grant Number: China Scholarship Council (CSC) scholarshipChina Scholarship Council; Cell and Molecular Biology Training Grant [NIH T32 GM08056]; SFARI Explored Award; Esther & Joseph Wolf Endowment Fund; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [T32GM008056] Funding Source: NIH RePORTER Funding text: MZ was supported by China Scholarship Council (CSC) scholarship. JN was supported by the Cell and Molecular Biology Training Grant (NIH T32 GM08056). Work in the Wynshaw-Boris Lab was supported by institutional funds, a SFARI Explored Award, and the Esther & Joseph Wolf Endowment Fund. AB - Background: Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been widely used to generate cellular models harboring specific disease-related genotypes. Of particular importance are ESC and iPSC applications capable of producing dorsal telencephalic neural progenitor cells (NPCs) that are representative of the cerebral cortex and overcome the challenges of maintaining a homogeneous population of cortical progenitors over several passages in vitro. While previous studies were able to derive NPCs from pluripotent cell types, the fraction of dorsal NPCs in this population is small and decreases over several passages. Here, we present three protocols that are highly efficient in differentiating mouse and human ESCs, as well as human iPSCs, into a homogeneous and stable population of dorsal NPCs. These protocols will be useful for modeling cerebral cortical neurological and neurodegenerative disorders in both mouse and human as well as for high-throughput drug screening for therapeutic development.Methods: We optimized three different strategies for generating dorsal telencephalic NPCs from mouse and human pluripotent cell types through single or double inhibition of bone morphogenetic protein (BMP) and/or SMAD pathways. Mouse and human pluripotent cells were aggregated to form embryoid bodies in suspension and were treated with dorsomorphin alone (BMP inhibition) or combined with SB431542 (double BMP/SMAD inhibition) during neural induction. Neural rosettes were then selected from plated embryoid bodies to purify the population of dorsal NPCs. We tested the expression of key dorsal NPC markers as well as nonectodermal markers to confirm the efficiency of our three methods in comparison to published and commercial protocols.Results: Single and double inhibition of BMP and/or SMAD during neural induction led to the efficient differentiation of dorsal NPCs, based on the high percentage of PAX6-positive cells and the NPC gene expression profile. There were no statistically significant differences in the variation of PAX6 and SOX1-positive NPCs between the two human pluripotent cell-derived methods; therefore, both methods are suitable for producing stable dorsal NPCs. When further differentiated into mature neurons, NPCs gave rise to a population of almost exclusively forebrain cortical neurons, confirming the dorsal fate commitment of the progenitors.Conclusions: The methods described in this study show improvements over previously published studies and are highly efficient at differentiating human and mouse pluripotent cell types into dorsal PAX6-positive NPCs and eventually into forebrain cortical neurons. LA - English DB - MTMT ER -