Mesenchymal Stem Cell-Derived Extracellular Vesicles for Tissue Repair Across Multiple Body Systems: A Narrative Review

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs), referred to as exosomes when meeting established size and biogenesis criteria, have emerged as cell-free therapeutic agents across diverse tissue systems. This narrative review synthesizes 40 peer-reviewed studies (2017-2026) identified through PubMed, evaluating MSC-EV activity across four body systems: orthopedic/musculoskeletal, neurological, cardiac, and integumentary (wound/skin). Across all four systems, MSC-derived EVs reduced tissue inflammation, suppressed apoptosis, promoted angiogenesis, and activated regenerative signaling cascades (Wnt/beta-catenin, PI3K/AKT, TGF-beta/Smad, Nrf2/HO-1). A preclinical meta-analysis of randomized animal MI trials reported a mean ejection-fraction improvement with MSC-derived EVs versus controls. GMP-compatible manufacturing processes including anion-exchange chromatography purification and lyophilization with trehalose have been validated. Umbilical cord and Wharton's Jelly-derived MSC-EVs are favorable sources given their accessibility and immunogenicity profile. The review supports advancement of MSC-derived EVs toward formal clinical investigation.