Abstract
Osteoarthritis (OA) is a degenerative joint condition leading to disability. The lack of effective treatment for OA creates a need for the development of new therapeutic approaches that may rely on stem cells including mesenchymal stem/stromal cells (MSCs) and their derivatives such as extracellular vesicles (EVs). The objective of this study was to evaluate the impact of MSCs derived from adipose tissue (AT-MSCs) and umbilical cord (UC-MSCs) and their EVs on cartilage-bone injury in vivo, to identify the specimen with the highest regenerative potential for further clinical applications in patients with OA. Humanized pigs underwent cartilage-bone injuries followed by intraarticular administration of products containing AT-MSCs, UC-MSCs, AT-MSC-EVs or UC-MSC-EVs mixed with hyaluronic acid (HA) or HA alone (for comparison). After 6-m follow-up, almost-fully-healed cartilage-bone defects were observed in the AT-MSC- and UC-MSC-treated pigs, and the defects were filled primarily with hyaline cartilage. In AT-MSC-EV- and UC-MSC-EV-treated pigs, a partial cartilage-bone tissue repair was observed, and the defects were filled primarily with fibrocartilage. The control pigs demonstrated limited regeneration capacity. The microcomputed tomography parameters of the subchondral bone indicated the ongoing progression of OA in controls, whereas in the MSC- and MSC-EV-treated pigs, the parameters indicated the cessation of OA progression. Moreover, no serious side effects were observed after the administration of products containing MSCs or MSC-EVs. The results indicate the safety and regenerative activity of MSCs on injured tissues, which favors not only the healing and improvement of bone structure but also the formation of hyaline cartilage. Superior tissue repair was observed after the administration of products containing AT-MSCs. The treatment of OA with MSC-EVs needs further standardization.