TY - JOUR AU - Kriston-Pál, Éva AU - Haracska, Lajos AU - Cooper, P. AU - Kiss-Tóth, E. AU - Szukacsov, Valéria AU - Monostori, Éva TI - A Regenerative Approach to Canine Osteoarthritis Using Allogeneic, Adipose-Derived Mesenchymal Stem Cells. Safety Results of a Long-Term Follow-Up JF - FRONTIERS IN VETERINARY SCIENCE J2 - FRONT VET SCI VL - 7 PY - 2020 SN - 2297-1769 DO - 10.3389/fvets.2020.00510 UR - https://m2.mtmt.hu/api/publication/31598021 ID - 31598021 N1 - Stem CellX Limited, Szeged, Hungary Institute of Genetics, Biological Research Centre, Szeged, Hungary Assentra Limited, Chelmsford, United Kingdom University of Sheffield, Department of Infection, Immunity Cardiovascular Disease, Sheffield, United Kingdom Export Date: 11 September 2020 Correspondence Address: Monostori, É.; Institute of Genetics, Biological Research CentreHungary; email: monostori.eva@brc.hu Stem CellX Limited, Szeged, Hungary Institute of Genetics, Biological Research Centre, Szeged, Hungary Assentra Limited, Chelmsford, United Kingdom University of Sheffield, Department of Infection, Immunity Cardiovascular Disease, Sheffield, United Kingdom Export Date: 6 October 2020 Correspondence Address: Monostori, É.; Institute of Genetics, Biological Research CentreHungary; email: monostori.eva@brc.hu Stem CellX Limited, Szeged, Hungary Institute of Genetics, Biological Research Centre, Szeged, Hungary Assentra Limited, Chelmsford, United Kingdom University of Sheffield, Department of Infection, Immunity Cardiovascular Disease, Sheffield, United Kingdom Export Date: 16 February 2021 Correspondence Address: Monostori, É.; Institute of Genetics, Hungary; email: monostori.eva@brc.hu Stem CellX Limited, Szeged, Hungary Institute of Genetics, Biological Research Centre, Szeged, Hungary Assentra Limited, Chelmsford, United Kingdom University of Sheffield, Department of Infection, Immunity Cardiovascular Disease, Sheffield, United Kingdom Export Date: 17 February 2021 Correspondence Address: Monostori, É.; Institute of Genetics, Hungary; email: monostori.eva@brc.hu Stem CellX Limited, Szeged, Hungary Institute of Genetics, Biological Research Centre, Szeged, Hungary Assentra Limited, Chelmsford, United Kingdom University of Sheffield, Department of Infection, Immunity Cardiovascular Disease, Sheffield, United Kingdom Export Date: 31 August 2021 Correspondence Address: Monostori, É.; Institute of Genetics, Hungary; email: monostori.eva@brc.hu AB - Mesenchymal stem cells (MSC) are emerging as an effective therapeutic tool in treating canine osteoarthritis (OA). In this report, we focused on the questions of whether MSC transplantation has long-term beneficial effects for the improvement in motion and also evaluated the safety of MSC injection. Visceral adipose tissue, a surgical waste obtained during routine ovariectomy served as a source of allogeneic MSCs and used to treat OA. Altogether, fifty-eight dogs were transplanted in the study suffering from OA in the elbow (42 animals), hip (5), knee (8), ankle (2), and hock (1). The effect of MSC transplantation was evaluated by the degree of lameness at a 4-5-years follow-up period based on the owners' subjective observations. The results showed that 83% of the OA patients improved or retained improvement in lameness. Clinical safety of the treatment was assessed by evaluating the coincidence of tumors or other diseases and other adverse reactions (such as local inflammation) after MSC cell therapy. Two incidences of local inflammation for <1 week at the site of injection were reported. No other adverse reactions were detected post-treatment. Sixteen dogs died during the study, 4 due to cancer and 12 due to other diseases, diagnosed by veterinarians. Overall, our survey suggests that MSC transplantation has long-term beneficial effects in reducing lameness. Moreover, no enrichment in a specific cause of death was observed in the transplanted animals, compared to reported literature. Our data suggest that MSC treatment could be an effective and safe long-term therapy for canine OA. © Copyright © 2020 Kriston-Pál, Haracska, Cooper, Kiss-Tóth, Szukacsov and Monostori. LA - English 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 - Fajka-Boja, Roberta AU - Suhajdáné Urbán, Veronika AU - Szebeni, Gábor AU - Czibula, Ágnes AU - Blaskó, Andrea AU - Kriston-Pál, Éva AU - Makra, Ildikó AU - Hornung, Ákos AU - Szabó, Enikő AU - Uher, Ferenc AU - Than, Nándor Gábor AU - Monostori, Éva TI - Galectin-1 is a local but not systemic immunomodulatory factor in mesenchymal stromal cells JF - CYTOTHERAPY J2 - CYTOTHERAPY VL - 18 PY - 2016 IS - 3 SP - 360 EP - 370 PG - 11 SN - 1465-3249 DO - 10.1016/j.jcyt.2015.12.004 UR - https://m2.mtmt.hu/api/publication/3024122 ID - 3024122 AB - BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) have powerful immunosuppressive activity. This function of MSCs is attributed to plethora of the expressed immunosuppressive factors, such as galectin-1 (Gal-1), a pleiotropic lectin with robust anti-inflammatory effect. Nevertheless, whether Gal-1 renders or contributes to the immunosuppressive effect of MSCs has not been clearly established. Therefore, this question was the focus of a complex study. METHODS: MSCs were isolated from bone marrows of wild-type and Gal-1 knockout mice and their in vitro anti-proliferative and apoptosis-inducing effects on activated T cells were examined. The in vivo immunosuppressive activity was tested in murine models of type I diabetes and delayed-type hypersensitivity. RESULTS: Both Gal-1-expressing and -deficient MSCs inhibited T-cell proliferation. Inhibition of T-cell proliferation by MSCs was mediated by nitric oxide but not PD-L1 or Gal-1. In contrast, MSC-derived Gal-1 triggered apoptosis in activated T cells that were directly coupled to MSCs, representing a low proportion of the T-cell population. Furthermore, absence of Gal-1 in MSCs did not affect their in vivo immunosuppressive effect. CONCLUSIONS: These results serve as evidence that Gal-1 does not play a role in the systemic immunosuppressive effect of MSCs. However, a local contribution of Gal-1 to modulation of T-cell response by direct cell-to-cell interaction cannot be excluded. Notably, this study serves a good model to understand how the specificity of a pleiotropic protein depends on the type and localization of the producing effector cell and its target. LA - English DB - MTMT ER - TY - JOUR AU - Hornung, Ákos AU - Deák, Magdolna AU - Novák, Julianna AU - E, Szabó AU - A, Czibula AU - R, Fajka-Boja AU - Kriston-Pál, Éva AU - Monostori, É AU - Kovács, László TI - Novel role for galectin-1 in T-cell apoptosis regulation and ist relevance to systemic lupus erythematosus JF - ANNALS OF THE RHEUMATIC DISEASES J2 - ANN RHEUM DIS VL - 74 PY - 2015 IS - Suppl. 1 SP - A19 EP - A19 SN - 0003-4967 DO - 10.1136/annrheumdis-2015-207259.44 UR - https://m2.mtmt.hu/api/publication/3040958 ID - 3040958 LA - English DB - MTMT ER - TY - JOUR AU - Szabó, Enikő AU - Fajka-Boja, Roberta AU - Kriston-Pál, Éva AU - Hornung, Ákos AU - Makra, Ildikó AU - Kudlik, Gyöngyi AU - Uher, Ferenc AU - Katona, Róbert László AU - Monostori, Éva AU - Czibula, Ágnes TI - Licensing by Inflammatory Cytokines Abolishes Heterogeneity of Immunosuppressive Function of Mesenchymal Stem Cell Population JF - STEM CELLS AND DEVELOPMENT J2 - STEM CELLS DEV VL - 24 PY - 2015 IS - 18 SP - 2171 EP - 2180 PG - 10 SN - 1547-3287 DO - 10.1089/scd.2014.0581 UR - https://m2.mtmt.hu/api/publication/2946565 ID - 2946565 N1 - Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, 62 Temesvári krt, Szeged, 6726, Hungary Stem Cell Biology Unit, National Blood Service, Budapest, Hungary Cited By :38 Export Date: 10 February 2021 CODEN: SCDTA Correspondence Address: Czibula, A.; Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, 62 Temesvári krt, Hungary AB - When mesenchymal stem cells (MSCs) are used for therapy of immunological pathologies, they get into an inflammatory environment, altering the effectiveness of the treatment. To establish the impact of environmental inflammatory factors on MSCs' immunofunction in the mirror of intrinsic heterogeneity of mouse MSC population, individual MSC clones were generated and characterized. Adipogenic but not osteogenic differentiation and pro-angiogenic activity of five independent MSC cell lines were similar. Regarding osteogenic differentiation, clones MSC3 and MSC6 exhibited poorer capacity than MSC2, MSC4, and MSC5. To study the immunosuppressive heterogeneity, in vitro and in vivo experiments have been carried out using T-cell proliferation assay and delayed-type hypersensitivity (DTH) response, respectively. A remarkable difference was found between the clones in their ability to inhibit T-cell proliferation in the following order: MSC2MSC5>MSC4>MSC3>>MSC6. Nevertheless, the differences between the immunosuppressive activities of the individual clones disappeared on pretreatment of the cells with pro-inflammatory cytokines, a procedure called licensing. Stimulation of all clones with IFN- and TNF- resulted in elevation of their inhibitory capability to a similar level. Nitric oxide (NO) and prostaglandin E2 (PGE2) were identified as major mediators of immunofunction of the MSC clones. The earlier findings were also supported by in vivo results. Without licensing, MSC2 inhibited DTH response, while MSC6 did not affect DTH response. In contrast, prestimulation of MSC6 with inflammatory cytokines resulted in strong suppression by this clone as well. Here, we have showed that MSC population is functionally heterogeneous in terms of immunosuppressive function; however, this variability is largely reduced under pro-inflammatory conditions. LA - English DB - MTMT ER - TY - JOUR AU - Deák, Magdolna AU - Hornung, Ákos AU - Novák, Julianna AU - Demydenko, Dmytro AU - Szabó, Enikő AU - Czibula, Ágnes AU - Fajka-Boja, Roberta AU - Kriston-Pál, Éva AU - Monostori, Éva AU - Kovács, László TI - Novel role for galectin-1 in T-cells under physiological and pathological conditions JF - IMMUNOBIOLOGY J2 - IMMUNOBIOLOGY VL - 220 PY - 2015 IS - 4 SP - 483 EP - 489 PG - 7 SN - 0171-2985 DO - 10.1016/j.imbio.2014.10.023 UR - https://m2.mtmt.hu/api/publication/2807186 ID - 2807186 N1 - Cited By :19 Export Date: 13 July 2022 CODEN: ZIMMD AB - Secreted, extracellular galectin-1 (exGal-1) but not intracellular Gal-1 (inGal-1) has been described as a strong immunosuppressive protein due to its major activity of inducing apoptosis of activated T-cells. It has previously been reported that T-cells express Gal-1 upon activation, however its participation in T-cell functions has remained largely elusive. To determine function of Gal-1 expressed by activated T-cells we have carried out a series of experiments. We have shown that Gal-1, expressed in Gal-1-transgenic Jurkat cells or in activated T-cells, remained intracellularly indicating that Gal-1-induced T-cell death was not a result of an autocrine effect of the de novo expressed Gal-1. Rather, a particular consequence of the inGal-1 expression was that T-cells became more sensitive to exGal-1 added either as a soluble protein or bound to the surface of a Gal-1-secreting effector cell. This was also verified when the susceptibility of activated T-cells from wild type or Gal-1 knockout mice to Gal-1-induced apoptosis were compared. Murine T-cells expressing Gal-1 were more sensitive to the cytotoxicity of the exGal-1 than their Gal-1 knockout counterparts. We also conducted a study with activated T-cells from patients with systemic lupus erythematosus (SLE), a disease in which dysregulated T-cell apoptosis has been well described. SLE T-cells expressed lower amounts of Gal-1 than healthy T-cells and were less sensitive to exGal-1. These results suggested a novel role of inGal-1 in T-cells as a regulator of T-cell response to exGal-1, and its likely contribution to the mechanism in T-cell apoptosis deficiency in lupus. LA - English DB - MTMT ER - TY - THES AU - Kriston-Pál, Éva TI - A mezenhimális őssejt-eredetű galektin-1 meghatározó faktor a felnőtt szöveti őssejtek pro-angiogén funkciójában PB - Szegedi Tudományegyetem (SZTE) PY - 2014 SP - 69 DO - 10.14232/phd.2340 UR - https://m2.mtmt.hu/api/publication/2729551 ID - 2729551 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Novák, Julianna AU - Kriston-Pál, Éva AU - Czibula, Ágnes AU - Deák, Magdolna AU - Kovács, László AU - Monostori, Éva AU - Fajka-Boja, Roberta TI - GM1 controlled lateral segregation of tyrosine kinase Lck predispose T-cells to cell-derived galectin-1-induced apoptosis. JF - MOLECULAR IMMUNOLOGY J2 - MOL IMMUNOL VL - 57 PY - 2014 IS - 2 SP - 302 EP - 309 PG - 8 SN - 0161-5890 DO - 10.1016/j.molimm.2013.10.010 UR - https://m2.mtmt.hu/api/publication/2459241 ID - 2459241 N1 - Cited By :8 Export Date: 13 July 2022 CODEN: IMCHA AB - One prominent immunoregulatory function of galectin-1 (Gal-1), a beta-galactoside binding mammalian lectin, is induction of apoptosis in activated T-cells by a process depending on the activity of Src family tyrosine kinase, Lck. Although the requirement for Lck in Gal-1 induced T-cell death and the ability of Gal-1 to affect the membrane localization of extracellular Gal-1-binding proteins have been well documented, the consequence of the complex and related reorganization of extra- and intracellular signaling components upon Gal-1 treatment of T-cells has not yet been revealed. Therefore, we have analyzed the plasma membrane movement of Lck upon Gal-1 triggered signaling, and the significance of this event in Gal-1 induced T-cell death. Non-receptor tyrosine kinase, Lck primarily localized in the synapse of tumor cell-T-cell during 15min of the established direct cell contact. Later, after 30min, a lateral segregation of Lck from the cell synapse was observed. The migration of Lck to the opposite of the cell contact apparently depended on the expression and cell surface presentation of Gal-1 on the effector (tumor) cells and was accompanied by phosphorylation on the negative regulatory tyrosine residue, Tyr505. Receptor tyrosine phosphatase, CD45 played crucial role in this event since CD45 deficiency or inhibition of its phosphatase activity resulted in the failure of Lck membrane movement. Level of the Gal-1-binding glycolipid GM1 ganglioside also essentially regulated Lck localization. Segregation of Lck and Gal-1 induced apoptosis was diminished in T-cells with low GM1 expression compared to T-cells with high GM1. Our results show that spatial regulation of Lck by CD45 and GM1 ganglioside determines the outcome of apoptotic response to Gal-1 and this local regulation may occur only upon intimate effector (Gal-1 expressing) cell-T-cell attachment. LA - English DB - MTMT ER - TY - JOUR AU - Hegedüs, Zsófia AU - Wéber, Edit AU - Kriston-Pál, Éva AU - Makra, Ildikó AU - Czibula, Ágnes AU - Monostori, Éva AU - Martinek, Tamás TI - Foldameric α/β-Peptide Analogs of the β-Sheet-Forming Antiangiogenic Anginex: Structure and Bioactivity JF - JOURNAL OF THE AMERICAN CHEMICAL SOCIETY J2 - J AM CHEM SOC VL - 135 PY - 2013 IS - 44 SP - 16578 EP - 16584 PG - 7 SN - 0002-7863 DO - 10.1021/ja408054f UR - https://m2.mtmt.hu/api/publication/2459240 ID - 2459240 AB - The principles of beta-sheet folding and design for alpha-peptidic sequences are well established, while those for sheet mimetics containing homologated amino acid building blocks are still under investigation. To reveal the structure-function relations of beta-amino-acid-containing foldamers, we followed a top-down approach to study a series of alpha/beta-peptidic analogs of anginex, a beta-sheet-forming antiangiogenic peptide. Eight anginex analogs were developed by systematic alpha --> beta(3) substitutions and analyzed by using NMR and CD spectroscopy. The foldamers retained the beta-sheet tendency, though with a decreased folding propensity. beta-Sheet formation could be induced by a micellar environment, similarly to that of the parent peptide. The destructuring effect was higher when the alpha --> beta(3) exchange was located in the beta-sheet core. Analysis of the beta-sheet stability versus substitution pattern and the local conformational bias of the bulky beta(3)V and beta(3)I residues revealed that a mismatch between the H-bonding preferences of the alpha- and beta-residues played a minor role in the structure-breaking effect. Temperature-dependent CD and NMR measurements showed that the hydrophobic stabilization was scaled-down for the alpha/beta-peptides. Analysis of the biological activity of the foldamer peptides showed that four anginex derivatives dose-dependently inhibited the proliferation of a mouse endothelial cell line. The alpha --> beta(3) substitution strategy applied in this work can be a useful approach to the construction of bioactive beta-sheet mimetics with a reduced aggregation tendency and improved pharmacokinetic properties. LA - English DB - MTMT ER - TY - JOUR AU - Szebeni, Gábor AU - Kriston-Pál, Éva AU - Blazsó, Péter AU - Katona, Róbert László AU - Novák, Julianna AU - Szabó, Enikő AU - Czibula, Ágnes AU - Fajka-Boja, Roberta AU - Hegyi, Beáta AU - Uher, Ferenc AU - Krenács, László AU - Joó, Gabriella AU - Monostori, Éva TI - Identification of Galectin-1 as a Critical Factor in Function of Mouse Mesenchymal Stromal Cell-Mediated Tumor Promotion JF - PLOS ONE J2 - PLOS ONE VL - 7 PY - 2012 IS - 7 PG - 13 SN - 1932-6203 DO - 10.1371/journal.pone.0041372 UR - https://m2.mtmt.hu/api/publication/2057717 ID - 2057717 AB - Bone marrow derived mesenchymal stromal cells (MSCs) have recently been implicated as one source of the tumor-associated stroma, which plays essential role in regulating tumor progression. In spite of the intensive research, the individual factors in MSCs controlling tumor progression have not been adequately defined. In the present study we have examined the role of galectin-1 (Gal-1), a protein highly expressed in tumors with poor prognosis, in MSCs in the course of tumor development. Co-transplantation of wild type MSCs with 4T1 mouse breast carcinoma cells enhances the incidence of palpable tumors, growth, vascularization and metastasis. It also reduces survival compared to animals treated with tumor cells alone or in combination with Gal-1 knockout MSCs. In vitro studies show that the absence of Gal-1 in MSCs does not affect the number of migrating MSCs toward the tumor cells, which is supported by the in vivo migration of intravenously injected MSCs into the tumor. Moreover, differentiation of endothelial cells into blood vessel-like structures strongly depends on the expression of Gal-1 in MSCs. Vital role of Gal-1 in MSCs has been further verified in Gal-1 knockout mice. By administering B16F10 melanoma cells into Gal-1 deficient animals, tumor growth is highly reduced compared to wild type animals. Nevertheless, co-injection of wild type but not Gal-1 deficient MSCs results in dramatic tumor growth and development. These results confirm that galectin-1 is one of the critical factors in MSCs regulating tumor progression. LA - English DB - MTMT ER -