Equine muscle-derived mesenchymal stem cells protect cartilage explants in osteoarthritis model: secretome characterization

Background: Osteoarthritis is a highly prevalent joint degenerative disease for which therapeutic treatments are limited or invasive. Cell therapy based on mesenchymal stem/stromal cells (MSCs) is therefore seen as a promising approach for this disease, in both human and horses. Objective: As the regenerative potential of MSCs is mainly conferred by paracrine function, the goal of this study is to characterize the secretome of muscle-derived MSCs (mdMSCs) in an in vitro model of OA to evaluate the clinical interest of mdMSCs as cell therapy for joint diseases like osteoarthritis. Methods: An equine osteoarthritis model composed of cartilage explants exposed to pro-inflammatory cytokines was first developed. Then, the effects of mdMSC coculture on cartilage explant were studied by measuring the glycosaminoglycan release and the NO2- production. To identify the underlying molecular actors, SILAC-based secretome analyses were conducted, in the presence of serum. The relative abundance of highly sequenced proteins was finally confirmed by western blot. Results: Co-culture with muscle-derived MSCs decreases the cytokine-induced glycosaminoglycan release by cartilage explants, suggesting a protecting effect of mdMSCs. Among the 52 equine proteins sequenced in the co-culture medium, the abundance of decorin and matrix metalloproteinase 3 was modified, as confirmed by western blot analyses. Conclusions: These results suggest that muscle-derived MSCs could reduce the catabolic effect of TNF and IL-1 on cartilage explant by decreasing the secretion and activity of Matrix Metalloproteinase 3 and increasing the decorin secretion