Mechanistic reprogramming by stem cell-derived extracellular vesicles: From cargo sorting to tissue regeneration

Stem cell-derived extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as potent bioactive mediators in regenerative medicine owing to their ability to transfer proteins, lipids, and nucleic acids that regulate intercellular communication and cellular homeostasis. This review provides a comprehensive and critical overview of stem cell-derived EVs, encompassing their classification, biogenesis pathways, isolation strategies, and characterization methodologies. Key EV separation techniques, including ultracentrifugation, size-exclusion chromatography, and immunoaffinity capture, are evaluated for efficiency, purity, and translational suitability. In parallel, state-of-the-art characterization approaches such as nanoparticle tracking analysis, electron microscopy, and mass spectrometry are discussed for their roles in defining EVs size distribution, morphology, and molecular cargo. Accumulating evidence highlights the substantial therapeutic potential of stem cell-derived EVs in diverse regenerative applications, including wound healing, cardiovascular repair, bone regeneration, and the treatment of neurological and metabolic disorders. Importantly, their low immunogenicity, enhanced safety profile, and minimal risk of tumorigenesis position EVs as a compelling alternative to conventional stem cell-based therapies. Collectively, this review synthesizes current advances in EV biology and technology, underscoring the promise of stem cell-derived EVs as next-generation, cell-free therapeutic platforms for regenerative medicine.