TY - JOUR AU - Marx, Anita AU - Osváth, Magdolna AU - Szikora, Bence AU - Pipek, Orsolya Anna AU - Csabai, István AU - Nagy, Ákos AU - Bödör, Csaba AU - Matula, Zsolt AU - Nagy, Ginette AU - Bors, András AU - Uher, Ferenc AU - Mikala, Gábor AU - Vályi-Nagy, István AU - Kacskovics, Imre TI - Liquid biopsy-based monitoring of residual disease in multiple myeloma by analysis of the rearranged immunoglobulin genes–A feasibility study JF - PLOS ONE J2 - PLOS ONE VL - 18 PY - 2023 IS - 5 PG - 23 SN - 1932-6203 DO - 10.1371/journal.pone.0285696 UR - https://m2.mtmt.hu/api/publication/33893006 ID - 33893006 N1 - * Megosztott szerzőség AB - The need for sensitive monitoring of minimal/measurable residual disease (MRD) in multiple myeloma emerged as novel therapies led to deeper responses. Moreover, the potential benefits of blood-based analyses, the so-called liquid biopsy is prompting more and more studies to assess its feasibility. Considering these recent demands, we aimed to optimize a highly sensitive molecular system based on the rearranged immunoglobulin (Ig) genes to monitor MRD from peripheral blood. We analyzed a small group of myeloma patients with the high-risk t(4;14) translocation, using next-generation sequencing of Ig genes and droplet digital PCR of patient-specific Ig heavy chain (IgH) sequences. Moreover, well established monitoring methods such as multiparametric flow cytometry and RT-qPCR of the fusion transcript IgH :: MMSET (IgH and multiple myeloma SET domain-containing protein) were utilized to evaluate the feasibility of these novel molecular tools. Serum measurements of M-protein and free light chains together with the clinical assessment by the treating physician served as routine clinical data. We found significant correlation between our molecular data and clinical parameters, using Spearman correlations. While the comparisons of the Ig-based methods and the other monitoring methods (flow cytometry, qPCR) were not statistically evaluable, we found common trends in their target detection. Regarding longitudinal disease monitoring, the applied methods yielded complementary information thus increasing the reliability of MRD evaluation. We also detected indications of early relapse before clinical signs, although this implication needs further verification in a larger patient cohort. LA - English DB - MTMT ER - TY - JOUR AU - Uher, Ferenc AU - Matula, Zsolt AU - Gönczi, Márton AU - Gopcsa, László AU - Bekő, Gabriella AU - Réti, Marienn Györgyi AU - Szekanecz, Zoltán AU - Ajzner, Éva AU - Vályi-Nagy, István TI - A súlyos akut légzőszervi szindrómát okozó koronavírus-2 elleni immunválasz JF - ORVOSI HETILAP J2 - ORV HETIL VL - 163 PY - 2022 IS - 20 SP - 774 EP - 787 PG - 14 SN - 0030-6002 DO - 10.1556/650.2022.32521 UR - https://m2.mtmt.hu/api/publication/32897456 ID - 32897456 AB - Coronavirus disease 2019 (COVID-19) displays tremendous inter-individual variability, ranging from asymptomatic infections to life-threatening illness. Although more studies are needed, a picture has begun to emerge that variability in the immune system components is a main contributor to the heterogeneous disease courses. Here, we provide a concept for the interaction of the innate and adaptive immune systems with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to link the observations that have been made during the first two years of the pandemic. Inborn errors of, and autoantibodies directed against, type I interferons, dysregulated myeloid response, hyperinflammation, lymphopenia, lymphocyte impairment, and heterogeneous adaptive immunity to SARS-CoV-2 are discussed, as well as their impact in the course of COVID-19. In addition, we will also review part of the key findings that have helped define and delineate some of the essential attributes of SARS-CoV-2-specific humoral and cell-mediated immune memory. Orv Hetil. 2022; 163(20): 774-787. LA - Hungarian DB - MTMT ER - TY - JOUR AU - Matula, Zsolt AU - Mikala, Gábor AU - Suhajdáné Urbán, Veronika AU - Vályi-Nagy, István AU - Uher, Ferenc TI - A vérképzőőssejt-niche szerepe a hematológiai neopláziák iniciációjában és progressziójában JF - HEMATOLÓGIA-TRANSZFUZIOLÓGIA J2 - HEMATOLÓGIA-TRANSZFUZIOLÓGIA VL - 51 PY - 2018 IS - 3 SP - 123 EP - 133 PG - 11 SN - 1786-5913 DO - 10.1556/2068.2018.51.3.3 UR - https://m2.mtmt.hu/api/publication/30407799 ID - 30407799 LA - Hungarian DB - MTMT ER - TY - BOOK AU - Uher, Ferenc TI - Őssejt-biológia ET - 0 PB - Medicina Könyvkiadó CY - Budapest PY - 2017 SP - 188 SN - 9789632266213 UR - https://m2.mtmt.hu/api/publication/3398186 ID - 3398186 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Kriston-Pál, Éva AU - Czibula, Ágnes AU - Gyuris, Z AU - Balka, Gyula AU - Seregi, A AU - Sükösd, Farkas AU - Süth, Miklós AU - Kiss-Tóth, E AU - Haracska, Lajos AU - Uher, Ferenc AU - Monostori, Éva TI - Characterization and therapeutic application of canine adipose mesenchymal stem cells to treat elbow osteoarthritis JF - CANADIAN JOURNAL OF VETERINARY RESEARCH-REVUE CANADIENNE DE RECHERCHE VETERINAIRE J2 - CAN J VET RES VL - 81 PY - 2017 IS - 1 SP - 73 EP - 78 PG - 6 SN - 0830-9000 UR - https://m2.mtmt.hu/api/publication/3190067 ID - 3190067 N1 - Funding Agency and Grant Number: [GINOP-2.3.2-15-2016-00020]; [GINOP-221-5-2016-00007] Funding text: The authors thank Karolina Korom and Marietta Gorog for collecting information from dogs' owners and liaising with the veterinarians involved in the program. We are grateful to the veterinarians, Drs. Otto Sebo (Small Animal Clinic, Mako), Peter Pal Muka (Profivet Veterinary Surgery Center and Animal Hospital, God), Peter Makai (MiniVet Small Animal Clinic, Budapest), Gyorgy Pelle (Teaching Animal Hospital, Nyiregyhaza), and Andras Banfi (PrimaVet Small Animal Clinic, Budapest), for surgery, transplantation, and supervision of the dogs. The authors also thank Akos Hornung for helpful advice about statistical evaluation and Mrs. Andrea Gercso and Katalin Kovacs for their excellent assistance. This work was supported by grants, GINOP-2.3.2-15-2016-00020 and GINOP-221-5-2016-00007. AB - Visceral adipose tissue (AT) obtained from surgical waste during routine ovariectomies was used as a source for isolating canine mesenchymal stem cells (MSCs). As determined by cytofluorimetry, passage 2 cells expressed MSC markers CD44 and CD90 and were negative for lineage-specific markers CD34 and CD45. The cells differentiated toward osteogenic, adipogenic, and chondrogenic directions. With therapeutic aims, 30 dogs (39 joints) suffering from elbow dysplasia (ED) and osteoarthritis (OA) were intra-articularly transplanted with allogeneic MSCs suspended in 0.5% hyaluronic acid (HA). A highly significant improvement was achieved without any medication as demonstrated by the degree of lameness during the follow-up period of 1 y. Control arthroscopy of 1 transplanted dog indicated that the cartilage had regenerated. Histological analysis of the cartilage biopsy confirmed that the regenerated cartilage was of hyaline type. These results demonstrate that transplantation of allogeneic adipose tissue-derived mesenchymal stem cells (AT-MSCs) is a novel, noninvasive, and highly effective therapeutic tool in treating canine elbow dysplasia. © 2017, Canadian Veterinary Medical Association. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Matula, Zsolt AU - Kudlik, Gyöngyi AU - Suhajdáné Urbán, Veronika AU - Uher, Ferenc TI - Quo vadis, hematológia? JF - ORVOSI HETILAP J2 - ORV HETIL VL - 157 PY - 2016 IS - 46 SP - 1819 EP - 1829 PG - 11 SN - 0030-6002 DO - 10.1556/650.2016.30580 UR - https://m2.mtmt.hu/api/publication/3139863 ID - 3139863 AB - For decades, developing hematopoietic cells have been strictly compartmentalized into a small population of multipotent self-renewing hematopoietic stem cells, multipotent hematopoietic progenitor cells that are undergoing commitment to myeloid or lymphoid fates, and unipotent precursor cells that mature towards peripheral blood and immune cells. Recent studies, however, have provided a battery of findings that cannot be explained by this "classical" hierarchical model for the architecture of hematopoiesis. It is emerging that heterogeneous hematopoietic stem cell populations in the bone marrow coexist, each with distinct, preprogrammed differentiation and proliferation behaviors. Three subsets can be distinguished among them: myeloid-biased (alpha), balanced (beta), and lymphoid-biased (gamma/delta) hematopoietic stem cells. The ratio of these hematopoietic stem cell subsets is developmentally regulated in the foetal liver and hematopoietic stem cells adult bone marrow, and coordinately gives rise to hematopoiesis. Beta- and gamma/delta-hematopoietic stem cells are found predominantly early in the life of an organism, whereas alpha-hematopoietic stem cells accumulate in aged mice and humans. In addition, new sophisticated genetic experiments in mice have identified a major role of long-lived, committed progenitor cells downstream from hematopoietic stem cells as drivers of normal adult hematopoiesis, and revealed that post-transplantation hematopoiesis differs qualitatively and quantitatively from normal steady-state hematopoiesis. These findings have important implications for understanding in situ the regulation of haematopoiesis in health and disease. Orv. Hetil., 2016, 157(46), 1819-1829. LA - Hungarian DB - MTMT ER - TY - JOUR AU - Dülk, Metta AU - Kudlik, Gyöngyi AU - Fekete, Anna AU - Ernszt, Dávid AU - Kvell, Krisztián AU - Pongrácz, Judit AU - Merő, Balázs László AU - Szeder, Bálint AU - Radnai, László AU - Geiszt, Miklós AU - Csecsy, DE AU - Kovács, Tamás AU - Uher, Ferenc AU - Lányi, Árpád AU - Vas, Virág AU - Buday, László TI - The scaffold protein Tks4 is required for the differentiation of mesenchymal stromal cells (MSCs) into adipogenic and osteogenic lineages JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 6 PY - 2016 PG - 9 SN - 2045-2322 DO - 10.1038/srep34280 UR - https://m2.mtmt.hu/api/publication/3124141 ID - 3124141 N1 - Megosztott első szerzőség AB - The commitment steps of mesenchymal stromal cells (MSCs) to adipogenic and other lineages have been widely studied but not fully understood. Therefore, it is critical to understand which molecules contribute to the conversion of stem cells into differentiated cells. The scaffold protein Tks4 plays a role in podosome formation, EGFR signaling and ROS production. Dysfunction of Tks4 causes a hereditary disease called Frank-ter Haar syndrome with a variety of defects concerning certain mesenchymal tissues (bone, fat and cartilage) throughout embryogenic and postnatal development. In this study, we aimed to analyze how the mutation of Tks4 affects the differentiation potential of multipotent bone marrow MSCs (BM-MSCs). We generated a Tks4 knock-out mouse strain on C57Bl/6 background, and characterized BM-MSCs isolated from wild type and Tks4-/- mice to evaluate their differentiation. Tks4-/- BM-MSCs had reduced ability to differentiate into osteogenic and adipogenic lineages compared to wild type. Studying the expression profile of a panel of lipid-regulated genes during adipogenic induction revealed that the expression of adipogenic transcription factors, genes responsible for lipid droplet formation, sterol and fatty acid metabolism was delayed or reduced in Tks4-/- BM-MSCs. Taken together, these results establish a novel function for Tks4 in the regulation of MSC differentiation. LA - English DB - MTMT ER - TY - JOUR AU - Kudlik, Gyöngyi AU - Hegyi, B AU - Czibula, Ágnes AU - Monostori, Éva AU - Buday, László AU - Uher, Ferenc TI - Mesenchymal stem cells promote macrophage polarization toward M2b-like cells. JF - EXPERIMENTAL CELL RESEARCH J2 - EXP CELL RES VL - 348 PY - 2016 IS - 1 SP - 36 EP - 45 PG - 10 SN - 0014-4827 DO - 10.1016/j.yexcr.2016.08.022 UR - https://m2.mtmt.hu/api/publication/3115599 ID - 3115599 N1 - Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary Stem Cell Biology Unit, National Blood Service, Budapest, Hungary Institute of Genetics, Biological Research Center of Hungarian Academy of Sciences, Szeged, Hungary Cited By :17 Export Date: 10 February 2021 CODEN: ECREA Correspondence Address: Uher, F.; National Blood Service, Karolina út 19-21., Hungary; email: uher.ferenc@gmail.com AB - Mesenchymal stem or stromal cells (MSCs) act on different components of the immune response including macrophages (MPhis). Therefore this study has been committed to explore how MSCs may modify the effect of MPhi polarization upon an inductive environment using mouse bone marrow (BM)-derived "naive", unpolarized MPhis. Phagocytosis of various MPhi subtypes was different since M1 and M2b showed poorer, while M2a higher rate of phagocytosis. MSCs significantly promoted yeast ingestion by M1 and M2b and diminished it by M2a cells. Under polarizing conditions, MSCs profoundly affected the TNFalpha production of MPhi subtypes since M1 and M2b MPhis produced less and M2a produced higher amount of TNFalpha while the amount of IL-10 was not affected. The most striking effect of MSCs was registered on M2b cells since the inflammatory TNFalpha dominance remarkably shifted to the immunosuppressive IL-10. Prepolarized M1 cells readily converted to M2a and M2b states when polarizing conditions changed from M1 to M2a or M2b induction, respectively. Repolarizing from M1 to M2a resulted in the decline of IL-10 and TNFalpha and defined elevation of Ym1 similar to levels characteristic to M2a primarily polarized from naive BM-MPhis. Similarly, polarization of M1 to M2b MPhis was successful showing increase in IL-10 and reduction in TNFalpha levels characteristic to M2b cells. However, when co-culturing with MSCs, M1-M2a or M1-M2b transition was not affected. Crosstalk between MPhis and MSCs depended on PGE-2 since COX-2 inhibition reduced the effect of MSCs to establish an IL-10-dominant cytokine production by MPhis. LA - English DB - MTMT ER - TY - JOUR AU - Szepesi, Áron AU - Matula, Zsolt AU - SZIGETI, A AU - Várady, György AU - Szalma, József AU - Szabó, Gyula AU - Uher, Ferenc AU - Sarkadi, Balázs AU - Német, Katalin TI - In vitro characterization of human mesenchymal stem cells isolated from different tissues with a potential to promote complex bone regeneration. JF - STEM CELLS INTERNATIONAL J2 - STEM CELLS INT VL - 2016 PY - 2016 PG - 9 SN - 1687-966X DO - 10.1155/2016/3595941 UR - https://m2.mtmt.hu/api/publication/3115524 ID - 3115524 LA - English DB - MTMT ER - TY - JOUR AU - Matula, Zsolt AU - Németh, Andrea AU - Lőrincz, Péter AU - Szepesi, Áron AU - Brózik, Anna AU - Buzás, Edit Irén AU - Lőw, Péter AU - Német, Katalin AU - Uher, Ferenc AU - Suhajdáné Urbán, Veronika TI - The role of extracellular vesicle and tunneling nanotube-mediated intercellular cross-talk between mesenchymal stem cells and human peripheral T cells. JF - STEM CELLS AND DEVELOPMENT J2 - STEM CELLS DEV VL - 25 PY - 2016 IS - 23 SP - 1818 EP - 1832 PG - 15 SN - 1547-3287 DO - 10.1089/scd.2016.0086 UR - https://m2.mtmt.hu/api/publication/3110431 ID - 3110431 N1 - Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, 1117, Hungary Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary Department of Anatomy, Cell and Developmental Biology, Eötvos Loránd University, Budapest, Hungary Creative Cell Ltd., Budapest, Hungary Stem Cell Biology, National Blood Service, Budapest, Hungary Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary Cited By :18 Export Date: 5 August 2019 CODEN: SCDTA Correspondence Address: Matula, Z.; Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of SciencesHungary; email: matula.zsolt@ttk.mta.hu Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, 1117, Hungary Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary Department of Anatomy, Cell and Developmental Biology, Eötvos Loránd University, Budapest, Hungary Creative Cell Ltd., Budapest, Hungary Stem Cell Biology, National Blood Service, Budapest, Hungary Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary Cited By :18 Export Date: 7 August 2019 CODEN: SCDTA Correspondence Address: Matula, Z.; Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of SciencesHungary; email: matula.zsolt@ttk.mta.hu Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, 1117, Hungary Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary Department of Anatomy, Cell and Developmental Biology, Eötvos Loránd University, Budapest, Hungary Creative Cell Ltd., Budapest, Hungary Stem Cell Biology, National Blood Service, Budapest, Hungary Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary Cited By :25 Export Date: 1 June 2020 CODEN: SCDTA Correspondence Address: Matula, Z.; Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of SciencesHungary; email: matula.zsolt@ttk.mta.hu Chemicals/CAS: gamma interferon, 82115-62-6 AB - The role of extracellular vesicles in mediating the immunosuppressory properties of mesenchymal stem cells has recently attracted remarkable scientific interest. The aim of this work was to analyze the transport mechanisms of membrane and cytoplasmic components between T lymphocytes and adipose tissue-derived mesenchymal stem cells, by focusing on the role of distinct populations of extracellular vesicles, direct cell-cell contacts and the soluble mediators per se in modulating T lymphocyte function. We found that neither murine thymocytes and human primary T cells, nor Jurkat lymphoblastoid cells incorporated appreciable amounts of MSC-derived microvesicles or exosomes. Moreover, these particles had no effect on the proliferation and IFN-gamma production of in vitro stimulated primary T cells. In contrast, AD-MSCs incorporated large amounts of membrane components from T cells as an intensive uptake of exosomes and microvesicles could be observed. Interestingly, we found a bi-directional exchange of cytoplasmic components between human AD-MSCs and primary T lymphocytes, mediated by tunneling nanotubes derived exclusively from the T cells. In contrast, tunneling nanotubes couldn't be observed between AD-MSCs and the Jurkat cells. Our results reveal a novel and efficient way of intercellular communication between MSCs and T cells, and may help a better understanding of the immunomodulatory function of MSCs. LA - English DB - MTMT ER -