Microenvironmental Modulation for Therapeutic Efficacy of Extracellular Vesicles.

Extracellular vesicles (EVs) hold significant promise for the prevention and treatment of various diseases. However, the translation of EV-based therapies into clinical practice faces considerable challenges, particularly in terms of production yield and therapeutic efficacy. Recent studies have emphasized the heterogeneity of EVs and the influence of parental cell microenvironmental signals on their biogenesis, cargo composition, and therapeutic outcomes. This review offers a comprehensive overview of strategies to optimize the therapeutic efficacy of EVs through physical, biochemical, and mechanical modulation. Additionally, it explores how microenvironmental signals affect EV cargoes and the mechanisms by which these signals can improve therapeutic efficacy. The review also addresses current challenges and potential solutions to accelerate the clinical translation of EV therapies. Ultimately, it highlights the potential of microenvironmental modulation in unlocking the full therapeutic capacity of EVs, providing key insights into their production and clinical use for treating various diseases.