Dr Hualien Tzu Chi Hospital, Tzu Chi University Hualien, Hualien, Taiwan (Republic of China)
Abstract: We investigated the therapeutic potential of miR-7704-modified extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (HUCMSCs) for osteoarthritis (OA) treatment. In vitro studies confirmed the successful transfection of miR-7704 into HUCMSCs and the subsequent isolation of EVs. In vivo experiments utilized an OA mouse model to evaluate the effects of intra-articular injection of these miR-7704-modified EVs. Outcomes assessed included walking capacity (rotarod test), cartilage morphology, histological scores, and the expression levels of type II collagen, aggrecan, interleukin-1 beta (IL-1β), and matrix metalloproteinase 13 (MMP13) in cartilage tissue. Characterization of the EVs verified their suitability for therapeutic application. Treatment with miR-7704-overexpressing EVs led to increased type II collagen and decreased MMP13 expression in IL-1β-treated chondrocytes in vitro. In vivo, the injection of miR-7704-modified EVs significantly enhanced walking capacity, preserved cartilage structure, and improved histological scores compared to controls. Additionally, the downregulation of MMP13 in treated cartilage suggested a potential mechanism underlying the therapeutic benefits observed. These findings highlight miR-7704-modified EVs derived from HUCMSCs as a promising therapeutic approach for OA. Future research should focus on optimizing dosing strategies, elucidating underlying mechanisms, ensuring safety and efficacy, improving delivery systems, and conducting early-phase clinical trials to establish the potential of HUCMSC-derived EVs for OA treatment.
