Abstract
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. 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. 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. 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.
Highlights
Osteoarthritis (OA), known as degenerative joint disease, is of major concern for human health
EASCs stored triglycerides in lipid droplets as shown by HCS LipidTOXTM Green neutral lipid staining and the expression of the transcription factor regulating adipogenesis PPARγ, which was significantly increased after 21 days of differentiation compared to day 0 (Figure 1D). equine ASCs (eASCs) differentiated into osteoblasts, as shown by Alizarin Red S staining and increased Runx2 expression at day 21 (Figure 1D)
They differentiated toward chondrocytes, as suggested by the presence of sulfated GAG evidenced by Safranin O staining and demonstrated by an enhanced expression of Sox9, Aggrecan, and Collagen type II markers (Figure 1D)
Summary
Osteoarthritis (OA), known as degenerative joint disease, is of major concern for human health. It is one of the most common orthopedic problems seen in horses. Clinical signs of disease are lameness, joint swelling, pain on flexion, or reduced activity, and, with time, these symptoms lead to structural joint alterations. Degradation of articular cartilage is a consequence of its poor capacity to repair and to withstand the cyclic trauma of athletic activity, and this is exacerbated with aging. Current treatments to control inflammation and pain and to stop disease progression include systemic non-steroidal anti-inflammatory drugs (NSAIDs), intra-articular steroids, viscosupplementation, and chondroprotectants [1, 2]. The economic impact of musculoskeletal disorders on the horse industry has stimulated many commercial companies to offer stem cell-based regenerative therapies for veterinary purposes [3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
