Exosomes (small extracellular vesicles, ~30–200 nm) are increasingly investigated as cell-free biologics because they transfer bioactive proteins, lipids, and nucleic acids that can reprogram recipient cells, while generally showing favorable tolerability compared with live-cell products. Interest initially surged in cosmetic and broad “regenerative” settings, but the current translational focus is shifting toward defined medical indications supported by controlled manufacturing and clinical trial oversight. Over the last few years, early-phase clinical programs have expanded into musculoskeletal joint disease, ocular surface and retinal disorders, cardiovascular repair, oncology, and immune-mediated inflammatory conditions. In osteoarthritis, intra-articular delivery of clinical-grade MSC-derived vesicles is now being tested clinically, with a growing pipeline of registered trials. In ophthalmology, secretome/extracellular vesicle-based products are advancing in persistent corneal epithelial defects and AMD-related programs. In oncology, engineered exosome platforms are entering first-in-human evaluation, including KRAS-targeted siRNA “iExosome” strategies in pancreatic cancer. Immunomodulatory exosome therapy is also transitioning into clinical testing in refractory inflammatory diseases, exemplified by trials in Crohn’s perianal fistulas. This mini-review summarizes key emerging indications and representative clinical trials (2022–2026), and outlines translational barriers, including standardization (MISEV), potency assays, scalable GMP manufacturing, biodistribution, and evolving regulatory expectations.
Mahdi Mahdipour (Wed,) studied this question.