Mesenchymal Stem Cells‐Derived Extracellular Vesicles in Orthopedic Diseases: Recent Advances and Therapeutic Potential

Abstract Ever since the first application of mesenchymal stem cell (MSC) transplantation treating human hematologic malignancies in 1995, MSC‐based treatments have demonstrated great therapeutic potential in clinical settings. However, only a few MSC‐based cell therapy products have been clinically approved. Accumulating evidence suggests that the beneficial effects of MSCs are mainly attributed to the release of paracrine factors or extracellular vesicles (EVs) rather than their mesodermal differentiation potential. Therefore, MSC‐derived EVs (MSC‐EVs), such as exosomes and microvesicles, have merged as promising alternatives to traditional cell‐based therapeutics in clinical practice. They offer several advantages such as better safety, lower immunogenicity, protection of cargoes from degradation, and the ability to overcome biological barriers. Moreover, there have been multiple clinical studies exploring the potential of MSC‐EVs for treating various diseases, including orthopedic disorders. However, there is no definitive “cure” for conditions such as osteoporosis and other bone disorders, but MSC‐EVs have displayed significant therapeutic potential for these orthopedic ailments. Therefore, the objective of this study is to conduct a systematic review of current knowledge related to MSC‐EVs and emphasize their potential application in treating orthopedic diseases, such as bone defects, osteoarthritis, osteoporosis, intervertebral disc degeneration, osteosarcoma, and osteoradionecrosis.