Effects of human umbilical cord mesenchymal stem cell-derived exosomes in the rat osteoarthritis models

Mesenchymal stem cells (MSCs) offer great potential for treatment of osteoarthritis (OA) by promoting articular cartilage regeneration via paracrine secretion of exosomes; however, the underlying mechanisms are not fully understood. This study aimed to explore the therapeutic effects of exosomes secreted by human umbilical cord-derived MSCs (hUC-MSCs) in rat models of OA and reveal the underlying mechanisms. UC-MSCs and UC-MSC-exosomes were prepared and identified by transmission electron microscopy and flow cytometry. IL-1 beta-induced OA chondrocytes and the operation and collagenase-induced OA rat models were established. The results of micro-computed tomography, histology, and immunohistochemistry showed that UC-MSC-exosomes promoted cartilage regeneration in OA rats. ELISA results showed that the levels of synovial fluid cytokines, TNF-alpha, IL-1 beta, and IL-6, were lower in exosome therapy group than control group in both OA rat models. Exosome treatment significantly downregulated the expression of MMP-13 and ADAMTS-5 in chondrocytes stimulated by IL-1 beta, and upregulated collagen II expression. These findings suggest that hUC-MSC-exosomes offer a promising option for the therapy for OA. Graphical AbstractExosomes secreted by human umbilical cord-derived mesenchymal stem cells promoted cartilage regeneration in OA rats. The levels of synovial fluid cytokines (TNF-alpha, IL-1 beta, and IL-6) were significantly reduced in the synovial fluid of exosome treated group, and exosome treatment also significantly downregulated the expression of MMP-13 and ADAMTS-5 in chondrocytes stimulated by IL-1 beta.