Therapeutic Potential of Extracellular Vesicles: From Biogenesis, Isolation and Molecular Characterization to Addressing Translational Gaps and Regulatory Barriers
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, Ali Mobasheri
Abstract
Extracellular vesicles (EVs) have emerged as essential mediators of intercellular communication, transporting a complex repertoire of lipids, proteins, and nucleic acids that mirror the physiological and pathological status of their parent cells. This review provides a comprehensive overview of EVs from their biogenesis and molecular composition to their translational potential in human disease. This review outlines the major classes of EVs, including exosomes, microvesicles, apoptotic bodies, and oncosomes, together with recent developments in their isolation, molecular characterization, and omics-based profiling. Special focus is given to the role of EVs in viral infection, inflammation, and immune regulation, as well as their contribution to disease development and cancer biology. Moreover, we highlight the emerging clinical applications of mesenchymal stem cell-derived EVs (MSC-EVs) in regenerative medicine and oncology, alongside the therapeutic modulation of EV signaling by photobiomodulation (PBM). Finally, we address key translational challenges related to standardization, scalability, and regulatory validation. As exosome-based therapeutics fall under strict FDA and EMA oversight, their translation further depends on harmonized quality controls and robust safety evaluation. By integrating molecular mechanisms with clinical applications, this review emphasizes the transformative potential of EVs as next-generation diagnostic and therapeutic tools in precision medicine.