Therapeutic small extracellular vesicles from key human stem and immune cellular sources: A review

Cell-to-cell communication is fundamental to life, with extracellular vesicles (EVs) playing a key role in intercellular signaling. Among them, small EVs (sEVs) have gained increasing attention as next-generation therapeutics. This review provides an overview of sEVs as therapeutic agents, comparing their advantages with cell-based and liposomal therapies, including unique benefits such as their enhanced ability to traverse biological barriers, ease of storage and administration, and their capability to utilize cellular machinery for fine-tuning therapeutic effects. Additionally, the therapeutic potential of sEVs from common human cell sources, including stem cells and immune cells, is discussed, highlighting their roles in modulating signaling pathways, cellular responses, and the microenvironment for treating cardiovascular, orthopedic, neurological, and autoimmune diseases, as well as cancer. Despite their promising outlook, challenges such as heterogeneity, extensive quality control requirements, systemic clearance, and scale-up limitations hinder clinical translation. Nonetheless, advancements in assay development, microfluidic models, computational databases, and bioengineering strategies continue to drive sEV-based therapies toward clinical and commercial viability.