Clinical Applications of Extracellular Vesicles: Promises and Pitfalls
Dragan Primorac, Petar Brlek, Luka Bulić, Nenad Hrvatin, Vedrana Škaro, Petar Projić, Martina Glavan, Ijeoma Oleru, Pierre Rocheteau, Carlo Tremolada, Ariana DeMers, Mary A. Ambach, Don Buford, Tamara Knežević, Dimitrios Kouroupis, Cole Conforti, D. Wood Kimbrough, R. Peter Schnorr, Lindsay Williams, Raminta Vaičiulevičiūtė, Žan Fortuna, Lara Oprešnik, Blaž Curk, Miomir Knežević, Gordana Kalan Živčec, Adelina Hrkać, Dimitrios Tsoukas, Ilona Uzielienè, Jolita Pachaleva, Eiva Bernotienė, Kristiana Barbato, Neep Patel, Isabella Demirdjian Guanche, EV Badiavas, Jana Mešić, Ana Medić Flajšman, Romina Milanič, Danijela Klarić, Vasiliki E Kalodimou, Massimo Allegri, Johannes Brachmann, Wei Seong Toh, Nancy Duarte Delgado, A. Mobasheri
Abstract
Extracellular vesicles (EVs) are membrane-bound nanoparticles released by almost all cell types into the extracellular space, acting as important mediators of intercellular communication by transferring proteins, lipids, and nucleic acids horizontally. EVs are generally classified into small EVs (<200 nm), medium/large EVs (>200 nm), microvesicles, and apoptotic bodies, with current classification methods focusing on physical properties, molecular composition, and cellular origin, as detailed in the MISEV2023 guidelines. EVs are highly promising for diagnostic and therapeutic applications due to their intrinsic biocompatibility, stability in biological fluids, capacity to carry diverse molecular cargo, and potential for drug delivery and functionalization to enable targeted delivery and tissue repair. This narrative review discusses the emerging roles of EVs across various medical fields, including obstetrics and gynecology, ophthalmology, otorhinolaryngology, urology, oncology, orthopedics, neurology, immunology, wound healing, chronic pain management, dermatology, and cardiology. In each discipline, EVs show potential as biomarkers for diagnosing physiological or pathological conditions and as carriers for targeted drug delivery and regenerative treatments. Exosomes, a major type of small EVs, have especially attracted attention as versatile nanocarriers for precision medicine. However, translation into clinical practice requires addressing key pitfalls, including the standardization of isolation and characterization protocols, dose definition, GMP-compliant large-scale production, and regulatory approval. Ongoing interdisciplinary collaboration across disciplines and thorough clinical testing will be essential to unlock the full biomedical potential of EVs and establish them as transformative tools in personalized healthcare.