Extracellular Vesicles As Therapeutic Resources in the Clinical Environment

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Feb 11

PMID 36768664

Authors

Jorge Sanz-Ros

Cristina Mas-Bargues

Nekane Romero-Garcia

Javier Huete-Acevedo

Mar Dromant

Consuelo Borras

Affiliations

Soon will be listed here.

Abstract

The native role of extracellular vesicles (EVs) in mediating the transfer of biomolecules between cells has raised the possibility to use them as therapeutic vehicles. The development of therapies based on EVs is now expanding rapidly; here we will describe the current knowledge on different key points regarding the use of EVs in a clinical setting. These points are related to cell sources of EVs, isolation, storage, and delivery methods, as well as modifications to the releasing cells for improved production of EVs. Finally, we will depict the application of EVs therapies in clinical trials, considering the impact of the COVID-19 pandemic on the development of these therapies, pointing out that although it is a promising therapy for human diseases, we are still in the initial phase of its application to patients.

Citing Articles

Extracellular Vesicles as Biomarkers in Infectious Diseases.

Cruz C, Sodawalla H, Mohanakumar T, Bansal S Biology (Basel). 2025; 14(2).

PMID: 40001950 PMC: 11851951. DOI: 10.3390/biology14020182.

Extracellular Vesicles as Mediators of Endothelial Dysfunction in Cardiovascular Diseases.

Jimenez-Trinidad F, Calvo-Gomez S, Sabate M, Brugaletta S, Campuzano V, Egea G Int J Mol Sci. 2025; 26(3).

PMID: 39940780 PMC: 11816526. DOI: 10.3390/ijms26031008.

Microvesicles Released by Osteoclastic Cells Exhibited Chondrogenic, Osteogenic, and Anti-Inflammatory Activities: An Evaluation of the Feasibility of Their Use for Treatment of Osteoarthritis in a Mouse Model.

Sheng M, Rundle C, Lau K Cells. 2025; 14(3).

PMID: 39936984 PMC: 11817440. DOI: 10.3390/cells14030193.

Melanoma-derived extracellular vesicles transfer proangiogenic factors.

Wilczak M, Surman M, PRZYBYlO M Oncol Res. 2025; 33(2):245-262.

PMID: 39866233 PMC: 11753996. DOI: 10.32604/or.2024.055449.

Emerging Strategies for Revascularization: Use of Cell-Derived Extracellular Vesicles and Artificial Nanovesicles in Critical Limb Ischemia.

Ravi Mythili V, Rajendran R, Arun R, Loganathbabu V, Reyaz D, Nagarajan A Bioengineering (Basel). 2025; 12(1).

PMID: 39851366 PMC: 11762151. DOI: 10.3390/bioengineering12010092.

References

Zhang S, Chu W, Lai R, Lim S, Hui J, Toh W . Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration. Osteoarthritis Cartilage. 2016; 24(12):2135-2140. DOI: 10.1016/j.joca.2016.06.022. View

Reiner A, Somoza V . Extracellular Vesicles as Vehicles for the Delivery of Food Bioactives. J Agric Food Chem. 2019; 67(8):2113-2119. DOI: 10.1021/acs.jafc.8b06369. View

Zhu Y, Shi M, Monsel A, Dai C, Dong X, Shen H . Nebulized exosomes derived from allogenic adipose tissue mesenchymal stromal cells in patients with severe COVID-19: a pilot study. Stem Cell Res Ther. 2022; 13(1):220. PMC: 9135389. DOI: 10.1186/s13287-022-02900-5. View

Thomi G, Surbek D, Haesler V, Joerger-Messerli M, Schoeberlein A . Exosomes derived from umbilical cord mesenchymal stem cells reduce microglia-mediated neuroinflammation in perinatal brain injury. Stem Cell Res Ther. 2019; 10(1):105. PMC: 6429800. DOI: 10.1186/s13287-019-1207-z. View

Mendt M, Kamerkar S, Sugimoto H, McAndrews K, Wu C, Gagea M . Generation and testing of clinical-grade exosomes for pancreatic cancer. JCI Insight. 2018; 3(8). PMC: 5931131. DOI: 10.1172/jci.insight.99263. View

Takahashi Y, Nishikawa M, Shinotsuka H, Matsui Y, Ohara S, Imai T . Visualization and in vivo tracking of the exosomes of murine melanoma B16-BL6 cells in mice after intravenous injection. J Biotechnol. 2013; 165(2):77-84. DOI: 10.1016/j.jbiotec.2013.03.013. View

Erdbrugger U, Blijdorp C, Bijnsdorp I, Borras F, Burger D, Bussolati B . Urinary extracellular vesicles: A position paper by the Urine Task Force of the International Society for Extracellular Vesicles. J Extracell Vesicles. 2021; 10(7):e12093. PMC: 8138533. DOI: 10.1002/jev2.12093. View

Sun I, Lerman L . Urinary Extracellular Vesicles as Biomarkers of Kidney Disease: From Diagnostics to Therapeutics. Diagnostics (Basel). 2020; 10(5). PMC: 7277956. DOI: 10.3390/diagnostics10050311. View

Takov K, Yellon D, Davidson S . Comparison of small extracellular vesicles isolated from plasma by ultracentrifugation or size-exclusion chromatography: yield, purity and functional potential. J Extracell Vesicles. 2019; 8(1):1560809. PMC: 6327926. DOI: 10.1080/20013078.2018.1560809. View

10.

Madison M, Roller R, Okeoma C . Human semen contains exosomes with potent anti-HIV-1 activity. Retrovirology. 2014; 11:102. PMC: 4245725. DOI: 10.1186/s12977-014-0102-z. View

11.

Thakur A, Sidu R, Zou H, Alam M, Yang M, Lee Y . Inhibition of Glioma Cells' Proliferation by Doxorubicin-Loaded Exosomes via Microfluidics. Int J Nanomedicine. 2020; 15:8331-8343. PMC: 7605152. DOI: 10.2147/IJN.S263956. View

12.

Cabeza L, Perazzoli G, Pena M, Cepero A, Luque C, Melguizo C . Cancer therapy based on extracellular vesicles as drug delivery vehicles. J Control Release. 2020; 327:296-315. DOI: 10.1016/j.jconrel.2020.08.018. View

13.

Couch Y, Buzas E, Di Vizio D, Gho Y, Harrison P, Hill A . A brief history of nearly EV-erything - The rise and rise of extracellular vesicles. J Extracell Vesicles. 2021; 10(14):e12144. PMC: 8681215. DOI: 10.1002/jev2.12144. View

14.

Mitragotri S . Modeling skin permeability to hydrophilic and hydrophobic solutes based on four permeation pathways. J Control Release. 2002; 86(1):69-92. DOI: 10.1016/s0168-3659(02)00321-8. View

15.

Guo M, Zhang K, Zhang J . Human Breast Milk-Derived Exosomal miR-148a-3p Protects Against Necrotizing Enterocolitis by Regulating p53 and Sirtuin 1. Inflammation. 2022; 45(3):1254-1268. DOI: 10.1007/s10753-021-01618-5. View

16.

Yenuganti V, Afroz S, Khan R, Bharadwaj C, Nabariya D, Nayak N . Milk exosomes elicit a potent anti-viral activity against dengue virus. J Nanobiotechnology. 2022; 20(1):317. PMC: 9258094. DOI: 10.1186/s12951-022-01496-5. View

17.

Hong P, Yang H, Wu Y, Li K, Tang Z . The functions and clinical application potential of exosomes derived from adipose mesenchymal stem cells: a comprehensive review. Stem Cell Res Ther. 2019; 10(1):242. PMC: 6686455. DOI: 10.1186/s13287-019-1358-y. View

18.

Ma B, Yang J, Song W, Ding R, Zhang Z, Ji H . Combining Exosomes Derived from Immature DCs with Donor Antigen-Specific Treg Cells Induces Tolerance in a Rat Liver Allograft Model. Sci Rep. 2016; 6:32971. PMC: 5027549. DOI: 10.1038/srep32971. View

19.

Imai T, Takahashi Y, Nishikawa M, Kato K, Morishita M, Yamashita T . Macrophage-dependent clearance of systemically administered B16BL6-derived exosomes from the blood circulation in mice. J Extracell Vesicles. 2015; 4:26238. PMC: 4323410. DOI: 10.3402/jev.v4.26238. View

20.

Sharma P, Mesci P, Carromeu C, McClatchy D, Schiapparelli L, Yates 3rd J . Exosomes regulate neurogenesis and circuit assembly. Proc Natl Acad Sci U S A. 2019; 116(32):16086-16094. PMC: 6689941. DOI: 10.1073/pnas.1902513116. View