Exosome: an Overview on Enhanced Biogenesis by Small Molecules

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Date 2025 Jan 25

PMID 39862264

Authors

Amir Bavafa

Maryam Izadpanahi

Elham Hosseini

Mehrdad Hajinejad

Mahsa Abedi

Fatemeh Forouzanfar

Sajad Sahab-Negah

Affiliations

Soon will be listed here.

Abstract

Exosomes are extracellular vesicles that received attention for their potential use in the treatment of various injuries. They communicate intercellularly by transferring genetic and bioactive molecules from parent cells. Although exosomes hold immense promise for treating neurodegenerative and oncological diseases, their actual clinical use is very limited because of their biogenesis and secretion. Recent studies have shown that small molecules can significantly enhance exosome biogenesis, thereby remarkably improving yield, functionality, and therapeutic effects. These molecules modulate critical pathways toward optimum exosome production in a mode that is either ESCRT dependent or ESCRT independent. Improved exosome biogenesis may provide new avenues for targeted cancer therapy, neuroprotection in neurodegenerative diseases, and regenerative medicine in wound healing. This review explores the role of small molecules in enhancing exosome biogenesis and secretion, highlights their underlying mechanisms, and discusses emerging clinical applications. By addressing current challenges and focusing on translational opportunities, this study provides a foundation for advancing cell-free therapies in regenerative medicine and beyond.

References

Abels E, Breakefield X . Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake. Cell Mol Neurobiol. 2016; 36(3):301-12. PMC: 5546313. DOI: 10.1007/s10571-016-0366-z. View

Abrami L, Brandi L, Moayeri M, Brown M, Krantz B, Leppla S . Hijacking multivesicular bodies enables long-term and exosome-mediated long-distance action of anthrax toxin. Cell Rep. 2013; 5(4):986-96. PMC: 3866279. DOI: 10.1016/j.celrep.2013.10.019. View

Abramowicz A, Story M . The Long and Short of It: The Emerging Roles of Non-Coding RNA in Small Extracellular Vesicles. Cancers (Basel). 2020; 12(6). PMC: 7352322. DOI: 10.3390/cancers12061445. View

Adamczyk K, Klein-Scory S, Tehrani M, Warnken U, Schmiegel W, Schnolzer M . Characterization of soluble and exosomal forms of the EGFR released from pancreatic cancer cells. Life Sci. 2011; 89(9-10):304-12. DOI: 10.1016/j.lfs.2011.06.020. View

Adell M, Migliano S, Upadhyayula S, Bykov Y, Sprenger S, Pakdel M . Recruitment dynamics of ESCRT-III and Vps4 to endosomes and implications for reverse membrane budding. Elife. 2017; 6. PMC: 5665648. DOI: 10.7554/eLife.31652. View

Adnan M, Islam W, Zhang J, Zheng W, Lu G . Diverse Role of SNARE Protein Sec22 in Vesicle Trafficking, Membrane Fusion, and Autophagy. Cells. 2019; 8(4). PMC: 6523435. DOI: 10.3390/cells8040337. View

Aguirre R, Kulkarni A, Becker M, Lei X, Sarkar S, Ramanadham S . Extracellular vesicles in β cell biology: Role of lipids in vesicle biogenesis, cargo, and intercellular signaling. Mol Metab. 2022; 63:101545. PMC: 9294332. DOI: 10.1016/j.molmet.2022.101545. View

Ahmad E, Rabbani G, Zaidi N, Azam Khan M, Qadeer A, Ishtikhar M . Revisiting ligand-induced conformational changes in proteins: essence, advancements, implications and future challenges. J Biomol Struct Dyn. 2012; 31(6):630-48. DOI: 10.1080/07391102.2012.706081. View

Ahmed I, Akram Z, Iqbal H, Munn A . The regulation of Endosomal Sorting Complex Required for Transport and accessory proteins in multivesicular body sorting and enveloped viral budding - An overview. Int J Biol Macromol. 2019; 127:1-11. DOI: 10.1016/j.ijbiomac.2019.01.015. View

10.

Akers J, Gonda D, Kim R, Carter B, Chen C . Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J Neurooncol. 2013; 113(1):1-11. PMC: 5533094. DOI: 10.1007/s11060-013-1084-8. View

11.

Alam M, Rahman M, Li Z . The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy. Genes Dis. 2023; 11(1):321-334. PMC: 10425812. DOI: 10.1016/j.gendis.2023.01.026. View

12.

Alcayaga-Miranda F, Varas-Godoy M, Khoury M . Harnessing the Angiogenic Potential of Stem Cell-Derived Exosomes for Vascular Regeneration. Stem Cells Int. 2016; 2016:3409169. PMC: 4834153. DOI: 10.1155/2016/3409169. View

13.

Almeria C, Kress S, Weber V, Egger D, Kasper C . Heterogeneity of mesenchymal stem cell-derived extracellular vesicles is highly impacted by the tissue/cell source and culture conditions. Cell Biosci. 2022; 12(1):51. PMC: 9063275. DOI: 10.1186/s13578-022-00786-7. View

14.

Alonso R, Rodriguez M, Pindado J, Merino E, Merida I, Izquierdo M . Diacylglycerol kinase alpha regulates the secretion of lethal exosomes bearing Fas ligand during activation-induced cell death of T lymphocytes. J Biol Chem. 2005; 280(31):28439-50. DOI: 10.1074/jbc.M501112200. View

15.

Alzhrani G, Alanazi S, Alsharif S, Albalawi A, Alsharif A, Abdel-Maksoud M . Exosomes: Isolation, characterization, and biomedical applications. Cell Biol Int. 2021; 45(9):1807-1831. DOI: 10.1002/cbin.11620. View

16.

Amini H, Rezabakhsh A, Heidarzadeh M, Hassanpour M, Hashemzadeh S, Ghaderi S . An Examination of the Putative Role of Melatonin in Exosome Biogenesis. Front Cell Dev Biol. 2021; 9:686551. PMC: 8219171. DOI: 10.3389/fcell.2021.686551. View

17.

An Y, Lin S, Tan X, Zhu S, Nie F, Zhen Y . Exosomes from adipose-derived stem cells and application to skin wound healing. Cell Prolif. 2021; 54(3):e12993. PMC: 7941238. DOI: 10.1111/cpr.12993. View

18.

Anang S, Kaushik N, Hingane S, Kumari A, Gupta J, Asthana S . Potent Inhibition of Hepatitis E Virus Release by a Cyclic Peptide Inhibitor of the Interaction between Viral Open Reading Frame 3 Protein and Host Tumor Susceptibility Gene 101. J Virol. 2018; 92(20). PMC: 6158408. DOI: 10.1128/JVI.00684-18. View

19.

Anguita E, Villalobo A . Ca signaling and Src-kinases-controlled cellular functions. Arch Biochem Biophys. 2018; 650:59-74. DOI: 10.1016/j.abb.2018.05.005. View

20.

Aslan C, Maralbashi S, Salari F, Kahroba H, Sigaroodi F, Kazemi T . Tumor-derived exosomes: Implication in angiogenesis and antiangiogenesis cancer therapy. J Cell Physiol. 2019; 234(10):16885-16903. DOI: 10.1002/jcp.28374. View