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Review

Clinical Applications of Extracellular Vesicles: Promises and Pitfalls

by
Dragan Primorac
1,2,3,4,5,6,7,8,9,10,11,
Petar Brlek
1,2,3,12,*,
Luka Bulić
1,2,3,
Nenad Hrvatin
1,13,
Vedrana Škaro
2,
Petar Projić
2,
Martina Glavan
14,
Ijeoma Oleru
14,
Pierre Rocheteau
15,
Carlo Tremolada
15,16,
Ariana DeMers
17,
Mary A. Ambach
18,
Don Buford
19,
Tamara Knežević
1,
Dimitrios Kouroupis
20,21,
Cole Conforti
20,21,
D. Wood Kimbrough
20,21,
R. Peter Schnorr
22,
Lindsay Williams
23,
Raminta Vaiciuleviciute
24,
Žan Fortuna
25,
Lara Oprešnik
25,
Blaž Curk
25,
Miomir Knežević
25,
Gordana Kalan Živčec
25,
Adelina Hrkać
1,
Dimitrios Tsoukas
26,
Ilona Uzieliene
27,
Jolita Pachaleva
27,
Eiva Bernotiene
27,
Kristiana Barbato
21,28,
Neep Patel
20,21,
Isabella Demirdjian Guanche
28,
Evangelos V. Badiavas
28,
Jana Mešić
1,3,
Ana Medić Flajšman
1,
Romina Milanič
1,
Danijela Klarić
1,
Vasiliki E. Kalodimou
29,
Massimo Allegri
30,
Johannes Brachmann
8,
Wei Seong Toh
31,32,
Nancy Duarte Delgado
33 and
Ali Mobasheri
27,33,34,35
add Show full author list remove Hide full author list
1
St. Catherine Specialty Hospital, 10000 Zagreb, Croatia
2
International Center for Applied Biological Research, 10000 Zagreb, Croatia
3
School of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia
4
Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia
5
Eberly College of Science, The Pennsylvania State University, State College, PA 16802, USA
6
School of Medicine, University of Split, 21000 Split, Croatia
7
The Henry C. Lee College of Criminal Justice and Forensic Sciences, University of New Haven, New Haven, CT 06516, USA
8
Sana Kliniken Oberfranken, 96450 Coburg, Germany
9
School of Medicine, University of Rijeka, 51000 Rijeka, Croatia
10
School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
11
Gandhinagar Campus, National Forensic Sciences University, Gandhinagar 382007, India
12
Department of Molecular Biology, Faculty of Science, University of Zagreb, 10000 Zagreb, Croatia
13
Department of Pediatrics, Clinical Hospital Center Rijeka, 51000 Rijeka, Croatia
14
Department of Neuroscience, Yale School of Medicine, Yale University, 333 Cedar Street, New Haven, CT 06510, USA
15
Exogems SA, Biopole, 1066 Epalinges, Switzerland
16
Image Regenerative Clinic, 20122 Milano, Italy
17
Restore Orthopedics and Sports Medicine, Sonora, CA 95370, USA
18
BioEvolve, San Diego Orthobiologics and Sports Center, San Diego, CA 92024, USA
19
Texas Orthobiologics, Dallas, TX 75204, USA
20
Department of Orthopaedics, UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, FL 33146, USA
21
Diabetes Research Institute, Cell Transplant Center, Miller School of Medicine, University of Miami, Miami, FL 33146, USA
22
FIRST Focused Integrated Regenerative Sports Medicine and Treatments, 8002 Zurich, Switzerland
23
Department of Immunology and Theranostics, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
24
State Research Institute Center for Innovative Medicine, LT-08406 Vilniaus, Lithuania
25
GaiaCell, Advanced Cell and Gene Therapy Ltd., Prevale 9, 1236 Trzin, Slovenia
26
Orthopaedic Clinic for Advanced Arthroscopic Sports and Regenerative Surgery Mitera Hospital, 15123 Athens, Greece
27
Department of Regenerative Medicine, State Research Institute Center for Innovative Medicine, LT-08406 Vilnius, Lithuania
28
Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, FL 91010, USA
29
Medical Innovation Center (MEDIC), School of Medicine, European University Cyprus, Diogenis Str., Engomi, Nicosia 2404, Cyprus
30
Centre Lémanique de Neuromodulation et Thérapie de la Douleur, Ensemble Hospitalier de la Côte (EHC), 1110 Morges, Switzerland
31
Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
32
Faculty of Dentistry, National University of Singapore, Singapore 117597, Singapore
33
Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, 90220 Oulu, Finland
34
Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China
35
Faculté de Médecine, Université de Liège, 4000 Liège, Belgium
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(3), 1509; https://doi.org/10.3390/ijms27031509
Submission received: 22 December 2025 / Revised: 16 January 2026 / Accepted: 28 January 2026 / Published: 3 February 2026
(This article belongs to the Section Molecular Biology)

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.
Keywords: extracellular vesicles; exosomes; biomarkers; targeted therapy; personalized medicine; regenerative medicine; clinical translation extracellular vesicles; exosomes; biomarkers; targeted therapy; personalized medicine; regenerative medicine; clinical translation

Share and Cite

MDPI and ACS Style

Primorac, D.; Brlek, P.; Bulić, L.; Hrvatin, N.; Škaro, V.; Projić, P.; Glavan, M.; Oleru, I.; Rocheteau, P.; Tremolada, C.; et al. Clinical Applications of Extracellular Vesicles: Promises and Pitfalls. Int. J. Mol. Sci. 2026, 27, 1509. https://doi.org/10.3390/ijms27031509

AMA Style

Primorac D, Brlek P, Bulić L, Hrvatin N, Škaro V, Projić P, Glavan M, Oleru I, Rocheteau P, Tremolada C, et al. Clinical Applications of Extracellular Vesicles: Promises and Pitfalls. International Journal of Molecular Sciences. 2026; 27(3):1509. https://doi.org/10.3390/ijms27031509

Chicago/Turabian Style

Primorac, Dragan, Petar Brlek, Luka Bulić, Nenad Hrvatin, Vedrana Škaro, Petar Projić, Martina Glavan, Ijeoma Oleru, Pierre Rocheteau, Carlo Tremolada, and et al. 2026. "Clinical Applications of Extracellular Vesicles: Promises and Pitfalls" International Journal of Molecular Sciences 27, no. 3: 1509. https://doi.org/10.3390/ijms27031509

APA Style

Primorac, D., Brlek, P., Bulić, L., Hrvatin, N., Škaro, V., Projić, P., Glavan, M., Oleru, I., Rocheteau, P., Tremolada, C., DeMers, A., Ambach, M. A., Buford, D., Knežević, T., Kouroupis, D., Conforti, C., Kimbrough, D. W., Schnorr, R. P., Williams, L., ... Mobasheri, A. (2026). Clinical Applications of Extracellular Vesicles: Promises and Pitfalls. International Journal of Molecular Sciences, 27(3), 1509. https://doi.org/10.3390/ijms27031509

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