Abstract
Age is the most important risk factor for degenerative diseases such as osteoarthritis (OA). It is associated with the accumulation of senescent cells in joint tissues that contribute to the pathogenesis of OA, in particular through the release of senescence-associated secretory phenotype (SASP) factors. Mesenchymal stromal cells (MSCs) and their derived extracellular vesicles (EVs) are promising treatments for OA. However, the senoprotective effects of MSC-derived EVs in OA have been poorly investigated. Here, we used EVs from human adipose tissue-derived MSCs (ASC-EVs) in two models of inflammaging (IL1β)-and DNA damage (etoposide)induced senescence in OA chondrocytes. We showed that the addition of ASC-EVs was effective in reducing senescence parameters, including the number of SA-β-Gal-positive cells, the accumulation of γH2AX foci in nuclei and the secretion of SASP factors. In addition, ASC-EVs demonstrated therapeutic efficacy when injected into a murine model of OA. Several markers of senescence, inflammation and oxidative stress were decreased shortly after injection likely explaining the therapeutic efficacy. In conclusion, ASC-EVs exert a senoprotective function both in vitro, in two models of induced senescence in OA chondrocytes and, in vivo, in the murine model of collagenase-induced OA.