ROLE OF MESENCHYMAL STEM CELL EXTRACELLULAR VESICLES IN CARTILAGE BIOLOGY AND THERAPY

Abstract

Knee and temporomandibular joints are complex load-bearing synovial joints that are commonly affected by injury and osteoarthritis. Studies have demonstrated the therapeutic efficacy of mesenchymal stem cells (MSCs) in treating joint diseases. Increasingly, the efficacy of MSCs is attributed to paracrine secretion, particularly exosomes. Here, we investigated the role of MSC exosomes in treating osteochondral defects and osteoarthritis in immunocompetent rat models. We observed that MSC exosomes mediated osteochondral regeneration by increasing cellular infiltration and proliferation, enhancing matrix synthesis and a regenerative immune phenotype. In osteoarthritic joint, MSC exosomes mediated an early suppression of pain and degeneration with reduced inflammation, followed by sustained proliferation that led to cartilage and subchondral bone regeneration. Using chondrocyte cultures, we could attribute these cellular processes partly to exosomal CD73-mediated adenosine activation of AKT, ERK and AMPK signalling. Together, these observations demonstrated the translational potential of a ready-to use cell-free exosome-based therapeutic for joint diseases.