Control of articular degeneration by extracellular vesicles from stem/stromal cells as a potential strategy for the treatment of osteoarthritis.

Osteoarthritis (OA) is a degenerative joint condition that contributes to years lived with disability. Current therapeutic approaches are limited as there are no disease-modifying interventions able to delay or inhibit the progression of disease. In recent years there has been an increasing interest in the immunomodulatory and regenerative properties of mesenchymal stem/stromal cells (MSCs) to develop new OA therapies. Extracellular vesicles (EVs) mediate many of the biological effects of these cells and may represent an alternative avoiding the limitations of cell-based therapy. There is also a growing interest in EV modifications to enhance their efficacy and applications. Recent preclinical studies have provided strong evidence supporting the potential of MSC EVs for the development of OA treatments. Thus, MSC EVs may regulate chondrocyte functions to avoid cartilage destruction, inhibit abnormal subchondral bone metabolism and synovial tissue alterations, and control pain behavior. EV actions may be mediated by the transfer of their cargo to target cells, with an important role for proteins and non-coding RNAs modulating signaling pathways relevant for OA progression. Nevertheless, additional investigations are needed concerning EV optimization, and standardization of preparation procedures. More research is also required for a better knowledge of possible effects on different OA phenotypes, pharmacokinetics, mechanism of action, long-term effects and safety profile. Furthermore, MSC EVs have a high potential as vehicles for drug delivery or as adjuvant therapy to potentiate or complement the effects of other approaches.