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Background Osteoarthritis (OA) 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. As the regenerative potential of MSCs is mainly conferred by paracrine function, the goal of this study was to characterize the secreted proteins of muscle-derived MSCs (mdMSCs) in an in vitro model of OA to evaluate the putative 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 co-culture on cartilage explant were studied by measuring the glycosaminoglycan release and the NO2− production. To identify the underlying molecular actors, stable isotope-labeling by amino acids in cell culture based secreted protein 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 conditioned medium, the abundance of decorin and matrix metalloproteinase 3 was significantly modified, as confirmed by western blot analyses. Conclusions These results suggest that muscle-derived MSCs could reduce the catabolic effect of TNFα and IL-1β on cartilage explant by decreasing the secretion and activity of matrix metalloproteinase 3 and increasing the decorin secretion. Graphical abstract mdMSCs capacity to reduce the catabolic consequences of cartilage exposure to pro-inflammatory cytokines. These effects can be explained by mdMSC-secreted bioactive such as TIMP-1 and decorin, known as an inhibitor of MMP3 and an anti-inflammatory protein, respectively.
Background Osteoarthritis (OA) 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. As the regenerative potential of MSCs is mainly conferred by paracrine function, the goal of this study was to characterize the secreted proteins of muscle-derived MSCs (mdMSCs) in an in vitro model of OA to evaluate the putative 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 co-culture on cartilage explant were studied by measuring the glycosaminoglycan release and the NO2− production. To identify the underlying molecular actors, stable isotope-labeling by amino acids in cell culture based secreted protein 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 conditioned medium, the abundance of decorin and matrix metalloproteinase 3 was significantly modified, as confirmed by western blot analyses. Conclusions These results suggest that muscle-derived MSCs could reduce the catabolic effect of TNFα and IL-1β on cartilage explant by decreasing the secretion and activity of matrix metalloproteinase 3 and increasing the decorin secretion. Graphical abstract mdMSCs capacity to reduce the catabolic consequences of cartilage exposure to pro-inflammatory cytokines. These effects can be explained by mdMSC-secreted bioactive such as TIMP-1 and decorin, known as an inhibitor of MMP3 and an anti-inflammatory protein, respectively.
The relevance of the work is related to the possibility of artificially adjusting the intensity of skeletal muscle tissue regeneration in animals, which will significantly affect the tactics of rehabilitation treatment of muscle injuries in the future. The purpose of the research was to determine the effectiveness of the transplanted mesenchymal stem cells on the recovery processes in experimentally injured rabbit muscles. The method of histological examination of microscopic changes in the experimentally damaged muscle tissue of the pelvic head of the biceps femoris muscle of rabbits was used. Microscopic studies of the regeneration process of experimentally damaged striated muscle tissue established that in animals after intramuscular injection of allogeneic mesenchymal stem cells, connective tissue developed around the defect on day 2 of the experiment. On day 4, a large number of stem cells were detected in the connective tissue at the site of muscle tissue damage. On day 6, only relatively small foci of muscle tissue regeneration were observed in this area. On day 8, only small focal accumulations of stem cells were detected in this location. On the 10th day after intramuscular injection of mesenchymal stem cells, newly developed muscle fibres appeared at the site of injury. On the 14th day after intramuscular injection of mesenchymal stem cells, fully developed muscle fibres and intermuscular connective tissue were observed at the site of injury. In rabbits, after intramuscular injection of allogeneic mesenchymal stem cells, all regenerative processes were more active than in animals of other experimental groups and were completely completed by day 14 of the experiment. The practical value of the results obtained is to clarify the patterns of development of reparative processes in the damaged muscle area and to determine the effectiveness of using transplanted allogeneic mesenchymal stem cells in stimulating recovery processes, which is important to consider in the treatment of muscle injuries using regenerative therapy
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