Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis

Abstract

Mesenchymal stem or stromal cells (MSCs) exert chondroprotective effects in preclinical models of osteoarthritis (OA). Most of their therapeutic effects are mediated via soluble mediators, which can be conveyed within extracellular vesicles (EVs). The objective of the study was to compare the respective role of exosomes (Exos) or microvesicles/microparticles (MPs) in OA. MPs and Exos were isolated from bone marrow murine BM-MSCs through differential centrifugation. Effect of MPs or Exos was evaluated on OA-like murine chondrocytes and chondroprotection was quantified by RT-qPCR. In OA-like chondrocytes, BM-MSC-derived MPs and Exos could reinduce the expression of chondrocyte markers (type II collagen, aggrecan) while inhibiting catabolic (MMP-13, ADAMTS5) and inflammatory (iNOS) markers. Exos and MPs were also shown to protect chondrocytes from apoptosis and to inhibit macrophage activation. In vivo, Exos or MPs were injected in the collagenase-induced OA (CIOA) model and histomorphometric analyses of joints were performed by µCT and confocal laser microscopy. BM-MSCs, MPs and Exos equally protected mice from joint damage. In conclusion, MPs and Exos exerted similar chondroprotective and anti-inflammatory function in vitro and protected mice from developing OA in vivo, suggesting that either Exos or MPs reproduced the main therapeutic effect of BM-MSCs.