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 (eASCs) and investigate the role of interferon-gamma (IFN gamma)-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, naive or IFN gamma-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 naive and IFN gamma-primed eASCs, but IFN gamma-priming enhanced these functions. In CIOA, intra-articular injection of eASCs prevented articular cartilage from degradation and IFN gamma-primed eASCs were more potent than naive cells. This effect was related to the modulation of eASC secretome by IFN gamma-priming. Conclusion: IFN gamma-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 IFN gamma-primed eASCs may have a therapeutic value for musculoskeletal diseases in veterinary medicine.