Stem cell-derived extracellular vesicles as a therapeutic for avascular necrosis: current status and future prospects

Avascular necrosis (AVN), also referred to as osteonecrosis (ON), is a major clinical challenge in orthopedic practice. Current treatment strategies include surgical options such as core decompression, as well as non-surgical approaches including statin therapy, weight reduction, and physiotherapy. Regenerative therapies - such as platelet-rich plasma injections, autologous bone marrow cell concentrates, and mesenchymal stem/stromal cells (MSCs), among others have shown some success. Although induced pluripotent stem cells (iPSCs) represent a promising source for cell therapy, their clinical application is restricted due to the risk of teratoma formation. In this context, the therapeutic potential of extracellular vesicles (EVs) secreted by stem cells has emerged as a relatively new area of investigation. This review summarizes findings from preclinical studies in animal models that have explored the use of MSC- and iPSC-derived EVs in the regenerative treatment of AVN/ON. Compared with MSC-EVs, the therapeutic use of iPSC-EVs has progressed more slowly, partly due to the high cost of expanding iPSCs to obtain a sufficient quantity of their EVs. Therefore, instead of using iPSC-derived EVs, the use of a cocktail of EVs secreted by iPSC-derived cellular derivatives may represent a safer, more cost-effective, and potentially more efficacious strategy for treating AVN.