International Journal of Molecular and Cellular Medicine (IJMCM)

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are a promising cell-free therapeutic in preclinical models of tendon healing. However, clinical translation remains to be demonstrated. MSC-EVs modulate two critical and interlinked processes in tendon repair inflammation and angiogenesis primarily via delivery of bioactive cargo such as microRNAs and proteins. In inflammation, MSC-EVs promote the transition of macrophages from a pro-inflammatory (M1) to an anti-inflammatory (M2) phenotype, enhancing the resolution of inflammation. In angiogenesis, MSC-EVs facilitate endothelial cell proliferation and migration, promoting early vascularization followed by vascular regression during later healing. Recent advancements in MSC-EVs engineering and delivery systems have improved their therapeutic efficacy, yet further research is essential to elucidate their molecular mechanisms and achieve precise therapeutic outcomes.