Objective. Osteoarthritis (OA) is a degenerative joint disease associated with chronic inflammation, pain and joint dysfunction. Studies have demonstrated the therapeutic efficacy of mesenchymal stem cell (MSC) therapies in OA. However, the efficacy of MSC therapies is increasingly attributed to paracrine secretion, particularly exosomes. Here, we examine the effects of MSC exosomes on pain, inflammation and joint degeneration in a surgically-induced rat OA model.
Methods. Exosomes were purified from human MSC conditioned medium by size fractionation. The anterior cruciate ligament transection (ACLT) procedure was performed on the right knee joints of 48 rats to induce OA over 4 weeks. Thereafter, the OA rats received weekly intra-articular injections of 10, 50 and 100 µg of exosomes or PBS (phosphate-buffered saline) as vehicle control. The remaining sham-operated 12 rats received PBS injections. Analyses were performed by weekly assessment of weight distribution, micro-computed tomography, histological assessment and scoring. Synovial fluid and plasma cytokine analyses were performed by multiplex cytokine assay.
Results. Weekly injections of MSC exosomes attenuated pain severity and progressive degradation of cartilage and subchondral bone induced by ACLT in a dose-dependent manner. By 8 weeks, exosome-treated rats (100µg) showed good joint restoration and pain recovery that approximated that of sham. These improvements were accompanied by suppressed local and systemic inflammation as evidenced by reduced levels of synovial and plasma pro-inflammatory cytokines. No adverse tissue reaction was observed in all the immunocompetent animals treated with MSC exosomes.
Conclusion. MSC exosomes could reduce OA joint pain and degeneration, possibly through modulation of local and systemic inflammation.