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Utility of a Mouse Model of Osteoarthritis to Demonstrate Cartilage Protection by IFNγ-Primed Equine Mesenchymal Stem Cells

OBJECTIVE: Mesenchymal stem cells isolated from adipose tissue (ASC) have been shown to influence the course of osteoarthritis (OA) in different animal models and are promising in veterinary medicine for horses involved in competitive sport. The aim of this study was to characterize equine ASCs (eAS...

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Autores principales: Maumus, Marie, Roussignol, Gautier, Toupet, Karine, Penarier, Geraldine, Bentz, Isabelle, Teixeira, Sandrine, Oustric, Didier, Jung, Mireille, Lepage, Olivier, Steinberg, Regis, Jorgensen, Christian, Noel, Danièle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037129/
https://www.ncbi.nlm.nih.gov/pubmed/27729913
http://dx.doi.org/10.3389/fimmu.2016.00392
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author Maumus, Marie
Roussignol, Gautier
Toupet, Karine
Penarier, Geraldine
Bentz, Isabelle
Teixeira, Sandrine
Oustric, Didier
Jung, Mireille
Lepage, Olivier
Steinberg, Regis
Jorgensen, Christian
Noel, Danièle
author_facet Maumus, Marie
Roussignol, Gautier
Toupet, Karine
Penarier, Geraldine
Bentz, Isabelle
Teixeira, Sandrine
Oustric, Didier
Jung, Mireille
Lepage, Olivier
Steinberg, Regis
Jorgensen, Christian
Noel, Danièle
author_sort Maumus, Marie
collection PubMed
description OBJECTIVE: Mesenchymal stem cells isolated from adipose tissue (ASC) have been shown to influence the course of osteoarthritis (OA) in different animal models and are promising in veterinary medicine for horses involved in competitive sport. The aim of this study was to characterize equine ASCs (eASCs) and investigate the role of interferon-gamma (IFNγ)-priming on their therapeutic effect in a murine model of OA, which could be relevant to equine OA. METHODS: ASC were isolated from subcutaneous fat. Expression of specific markers was tested by cytometry and RT-qPCR. Differentiation potential was evaluated by histology and RT-qPCR. For functional assays, naïve or IFNγ-primed eASCs were cocultured with peripheral blood mononuclear cells or articular cartilage explants. Finally, the therapeutic effect of eASCs was tested in the model of collagenase-induced OA (CIOA) in mice. RESULTS: The immunosuppressive function of eASCs on equine T cell proliferation and their chondroprotective effect on equine cartilage explants were demonstrated in vitro. Both cartilage degradation and T cell activation were reduced by naïve and IFNγ-primed eASCs, but IFNγ-priming enhanced these functions. In CIOA, intra-articular injection of eASCs prevented articular cartilage from degradation and IFNγ-primed eASCs were more potent than naïve cells. This effect was related to the modulation of eASC secretome by IFNγ-priming. CONCLUSION: IFNγ-priming of eASCs potentiated their antiproliferative and chondroprotective functions. We demonstrated that the immunocompetent mouse model of CIOA was relevant to test the therapeutic efficacy of xenogeneic eASCs for OA and confirmed that IFNγ-primed eASCs may have a therapeutic value for musculoskeletal diseases in veterinary medicine.
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spelling pubmed-50371292016-10-11 Utility of a Mouse Model of Osteoarthritis to Demonstrate Cartilage Protection by IFNγ-Primed Equine Mesenchymal Stem Cells Maumus, Marie Roussignol, Gautier Toupet, Karine Penarier, Geraldine Bentz, Isabelle Teixeira, Sandrine Oustric, Didier Jung, Mireille Lepage, Olivier Steinberg, Regis Jorgensen, Christian Noel, Danièle Front Immunol Immunology OBJECTIVE: Mesenchymal stem cells isolated from adipose tissue (ASC) have been shown to influence the course of osteoarthritis (OA) in different animal models and are promising in veterinary medicine for horses involved in competitive sport. The aim of this study was to characterize equine ASCs (eASCs) and investigate the role of interferon-gamma (IFNγ)-priming on their therapeutic effect in a murine model of OA, which could be relevant to equine OA. METHODS: ASC were isolated from subcutaneous fat. Expression of specific markers was tested by cytometry and RT-qPCR. Differentiation potential was evaluated by histology and RT-qPCR. For functional assays, naïve or IFNγ-primed eASCs were cocultured with peripheral blood mononuclear cells or articular cartilage explants. Finally, the therapeutic effect of eASCs was tested in the model of collagenase-induced OA (CIOA) in mice. RESULTS: The immunosuppressive function of eASCs on equine T cell proliferation and their chondroprotective effect on equine cartilage explants were demonstrated in vitro. Both cartilage degradation and T cell activation were reduced by naïve and IFNγ-primed eASCs, but IFNγ-priming enhanced these functions. In CIOA, intra-articular injection of eASCs prevented articular cartilage from degradation and IFNγ-primed eASCs were more potent than naïve cells. This effect was related to the modulation of eASC secretome by IFNγ-priming. CONCLUSION: IFNγ-priming of eASCs potentiated their antiproliferative and chondroprotective functions. We demonstrated that the immunocompetent mouse model of CIOA was relevant to test the therapeutic efficacy of xenogeneic eASCs for OA and confirmed that IFNγ-primed eASCs may have a therapeutic value for musculoskeletal diseases in veterinary medicine. Frontiers Media S.A. 2016-09-27 /pmc/articles/PMC5037129/ /pubmed/27729913 http://dx.doi.org/10.3389/fimmu.2016.00392 Text en Copyright © 2016 Maumus, Roussignol, Toupet, Penarier, Bentz, Teixeira, Oustric, Jung, Lepage, Steinberg, Jorgensen and Noel. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Maumus, Marie
Roussignol, Gautier
Toupet, Karine
Penarier, Geraldine
Bentz, Isabelle
Teixeira, Sandrine
Oustric, Didier
Jung, Mireille
Lepage, Olivier
Steinberg, Regis
Jorgensen, Christian
Noel, Danièle
Utility of a Mouse Model of Osteoarthritis to Demonstrate Cartilage Protection by IFNγ-Primed Equine Mesenchymal Stem Cells
title Utility of a Mouse Model of Osteoarthritis to Demonstrate Cartilage Protection by IFNγ-Primed Equine Mesenchymal Stem Cells
title_full Utility of a Mouse Model of Osteoarthritis to Demonstrate Cartilage Protection by IFNγ-Primed Equine Mesenchymal Stem Cells
title_fullStr Utility of a Mouse Model of Osteoarthritis to Demonstrate Cartilage Protection by IFNγ-Primed Equine Mesenchymal Stem Cells
title_full_unstemmed Utility of a Mouse Model of Osteoarthritis to Demonstrate Cartilage Protection by IFNγ-Primed Equine Mesenchymal Stem Cells
title_short Utility of a Mouse Model of Osteoarthritis to Demonstrate Cartilage Protection by IFNγ-Primed Equine Mesenchymal Stem Cells
title_sort utility of a mouse model of osteoarthritis to demonstrate cartilage protection by ifnγ-primed equine mesenchymal stem cells
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037129/
https://www.ncbi.nlm.nih.gov/pubmed/27729913
http://dx.doi.org/10.3389/fimmu.2016.00392
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