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Organoid-derived extracellular vesicles: From organoid, to organoid

Ting Cheng1,2,3,4 ,  Wojciech Chrzanowski5* ,  Han Liu1,2,3,4,6,7* ,  Jiacan Su1,2,3,4,8*
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1 Institute of Translational Medicine, Shanghai University, Shanghai, China
2 MedEng-X Institutes, Shanghai University, Shanghai, China
3 Organoid Research Center, Shanghai University, Shanghai, China
4 National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, China
5 Faculty of Medicine and Health, Sydney School of Pharmacy, Sydney Nano Institute, The University of Sydney, Camperdown, Australia
6 Su Zhou Innovation Center of Shanghai University, Suzhou, Jiangsu, China
7 Sanming Second Hospital, Sanming, Fujian, China
8 Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
OR 2025, 1(4), 025450031 https://doi.org/10.36922/OR025450031
Received: 5 November 2025 | Revised: 24 December 2025 | Accepted: 25 December 2025 | Published online: 30 December 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Organoids are models of miniature organs formed by three-dimensional (3D) culture of stem cells or primary tissue cells. Their structure or function is highly similar to that of in-situ organs. Extracellular vesicles (EVs) are non-replicating nanocarriers with a phospholipid bilayer (20 - 400 nanometers) used to deliver bioactive substances. Organoid-derived extracellular vesicles (OEVs) are easier to form than conventional EVs and have enhanced biological functions. Organoids have the characteristics of stem cells; the transportation of bioactive substances by OEVs has broad prospects in medical applications. This article expounds the development, concept, construction methods and applications of organoids, describes the types, research progress and advantages of EVs, then outlines the concept of the basic biology of EVs, and explores their potential applications in disease treatment and intervention. Furthermore, we examine the distinctions that differentiate OEVs from conventional EVs. Finally, this paper summarises the advantages and challenges of OEVs and outlines their future prospects in disease treatment. 

Graphical abstract
Keywords
Organoids
Organoid-derived extracellular vesicles
Cell-free therapy
Regenerative medicine
Funding
This work was supported by the National Natural Science Foundation of China (82202344), Jiangsu Province Natural Science Foundation project (BK20241808), Fujian Province Natural Science Foundation project (2024J01221), and Jiangsu Province Youth Science and Technology Talent Support Project (JSTJ-2024-097).
Conflict of interest
Jiacan Su is one of the Editors-in-Chief of this journal, but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. The authors declare they have no competing interests.
References
  1. Cano A, Ettcheto M, Bernuz M, et al. Extracellular vesicles, the emerging mirrors of brain physiopathology. Int J Biol Sci. 2023;19(3):721-743. doi: 10.7150/ijbs.79063

 

  1. Doyle LM, Wang MZ. Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells. 2019;8(7):727. doi: 10.3390/cells8070727

 

  1. Liu H, Geng Z, Su J. Engineered mammalian and bacterial extracellular vesicles as promising nanocarriers for targeted therapy. Extracell Vesicles Circ Nucleic Acids. 2022;3(2):63. doi: 10.20517/evcna.2022.04

 

  1. Maas S L N, Breakefield X O, Weaver A M. Extracellular vesicles: unique intercellular delivery vehicles. Trends Cell Biol. 2017;27(3):172-188. doi: 10.1016/j.tcb.2016.11.003

 

  1. Kumar M A, Baba S K, Sadida H Q, et al. Extracellular vesicles as tools and targets in therapy for diseases. Signal Transduct Target Ther. 2024;9(1):27. doi: 10.1038/s41392-024-01735-1

 

  1. Chutkan H, Macdonald I, Manning A, Kuehn MJ. Quantitative and qualitative preparations of bacterial outer membrane vesicles. Methods Mol Biol. 2013;966:259-272. doi: 10.1007/978-1-62703-245-2-16

 

  1. Ji N, Wang F, Wang M, Zhang W, Liu H, Su J. Engineered bacterial extracellular vesicles for central nervous system diseases. J Control Release. 2023;364:46-60. doi: 10.1016/j.jconrel.2023.10.027

 

  1. Su Y, Sun X, Liu X, et al. hUC-EVs-ATO reduce the severity of acute GVHD by resetting inflammatory macrophages toward the M2 phenotype. J Hematol Oncol. 2022;15(1):99. Published 2022 Jul 21. doi: 10.1186/s13045-022-01315-2

 

  1. Zaborowski M Ł P, Balaj L, Breakefield X O, Lai C P. Extracellular vesicles: composition, biological relevance, and methods of study. Bioscience. 2015;65(8):783-797. doi: 10.1093/biosci/biv084

 

  1. Zhou G, Li R, Sheng S, et al. Organoids and organoid extracellular vesicles-based disease treatment strategies. J Nanobiotechnol. 2024;22(1):679. doi: 10.1186/s12951-024-02917-3

 

  1. Yi S A, Zhang Y, Rathnam C, et al. Bioengineering approaches for the advanced organoid research. Adv Mater. 2021;33(45):2007949. doi: 10.1002/adma.202007949

 

  1. Rossi G, Manfrin A, Lutolf M P. Progress and potential in organoid research. Nat Rev Genet. 2018;19(11):671-687. doi: 10.1038/s41576-018-0051-9

 

  1. Garreta E, Kamm R D, Chuva de Sousa Lopes S M, et al. Rethinking organoid technology through bioengineering. Nat Mater. 2021;20(2):145-155. doi: 10.1038/s41563-020-00804-4

 

  1. Mei J, Liu X, Tian HX, et al. Tumour organoids and assembloids: Patient-derived cancer avatars for immunotherapy. Clin Transl Med. 2024;14(4):e1656. doi: 10.1002/ctm2.1656

 

  1. Jiang X, Oyang L, Peng Q, et al. Organoids: opportunities and challenges of cancer therapy. Front Cell Dev Biol. 2023;11:1232528. doi: 10.3389/fcell.2023.1232528

 

  1. Yang Q, Li M, Yang X, et al. Flourishing tumor organoids: History, emerging technology, and application. Bioeng Transl Med. 2023;8(5):e10559. doi: 10.1002/btm2.10559

 

  1. Sakaguchi H. Self-organization and applications of neural organoids. Eur J Cell Biol. 2025;104(2):151496. doi: 10.1016/j.ejcb.2025.151496

 

  1. Bai L, Wu Y, Li G, Zhang W, Zhang H, Su J. AI-enabled organoids: Construction, analysis, and application. Bioact Mater. 2023;31:525-548. doi: 10.1016/j.bioactmat.2023.09.005

 

  1. Srivastava V, Huycke TR, Phong KT, Gartner ZJ. Organoid models for mammary gland dynamics and breast cancer. Curr Opin Cell Biol. 2020;66:51-58. doi: 10.1016/j.ceb.2020.05.003

 

  1. Liang X, Li C, Song J, et al. HucMSC-Exo Promote Mucosal Healing in Experimental Colitis by Accelerating Intestinal Stem Cells and Epithelium Regeneration via Wnt Signaling Pathway. Int J Nanomedicine. 2023;18:2799-2818. doi: 10.2147/IJN.S402179

 

  1. Liu H, Song P, Zhang H, et al. Synthetic biology-based bacterial extracellular vesicles displaying BMP-2 and CXCR4 to ameliorate osteoporosis. J Extracell Vesicles. 2024;13(4):e12429. doi: 10.1002/jev2.70095

 

  1. Yang Y, Kong Y, Cui J, et al. Advances and applications of cancer organoids in drug screening and personalized medicine. Stem Cell Rev Rep. 2024;20(5):1213-1226. doi: 10.1007/s12015-024-10714-6

 

  1. Corrò C, Novellasdemunt L, Li V S W. A brief history of organoids. Am J Physiol Cell Physiol. 2020;319(3): C575-C582. doi: 10.1152/ajpcell.00120.2020

 

  1. Verstegen M M A, Coppes R P, Beghin A, et al. Clinical applications of human organoids. Nat Med. 2025;31(2): 409-421. doi: 10.1038/s41591-024-03489-3

 

  1. Tang X Y, Wu S, Wang D, et al. Human organoids in basic research and clinical applications. Signal Transduct Target Ther. 2022;7(1):168. doi: 10.1038/s41392-022-01024-9

 

  1. Gopallawa I, Gupta C, Jawa R, et al. Applications of organoids in advancing drug discovery and development. J Pharm Sci. 2024;113(9):2659-2667. doi: 10.1016/j.xphs.2024.06.016

 

  1. Hong Z X, Zhu S T, Li H, et al. Bioengineered skin organoids: from development to applications. Mil Med Res. 2023;10(1):40. doi: 10.1186/s40779-023-00475-7

 

  1. Clevers H. Modeling development and disease with organoids. Cell. 2016;165(7):1586-1597. doi: 10.1016/j.cell.2016.05.082

 

  1. Liu H, Zhang Q, Wang S, et al. Bacterial extracellular vesicles as bioactive nanocarriers for drug delivery: advances and perspectives. Bioact Mater. 2022;14:169-181. doi: 10.1016/j.bioactmat.2021.12.006

 

  1. Record M, Carayon K, Poirot M, et al. Exosomes as new vesicular lipid transporters involved in cell-cell communication and various pathophysiologies. Biochim Biophys Acta. 2014;1841(1):108-120. doi: 10.1016/j.bbalip.2013.10.004

 

  1. Schwechheimer C, Kuehn M J. Outer-membrane vesicles from Gram-negative bacteria: biogenesis and functions. Nat Rev Microbiol. 2015;13(10):605-619. doi: 10.1038/nrmicro3525

 

  1. Pérez-Cruz C, Delgado L, López-Iglesias C, et al. Outer-inner membrane vesicles naturally secreted by gram-negative pathogenic bacteria. PLoS One. 2015;10(1):e0116896. doi: 10.1371/journal.pone.0116896

 

  1. Almousa S, Kim S, Kumar A, et al. Bacterial nanovesicles as interkingdom signaling moieties mediating pain hypersensitivity. ACS Nano. 2025;19(3):3210-3225. doi: 10.1021/acsnano.4c10529

 

  1. Xu H, Li W, Yue H, et al. S100B induces angiogenesis via the clathrin/FOXO1/β-catenin signaling pathway and contributes to Bevacizumab resistance in epithelial ovarian cancer. J Adv Res. doi: 10.1016/j.jare.2025.05.060

 

  1. Moghaddam ZS, Dehghan A, Halimi S, et al. Bacterial Extracellular Vesicles: Bridging Pathogen Biology and Therapeutic Innovation. Acta Biomater. 2025;200:1-20. doi: 10.1016/j.actbio.2025.05.028

 

  1. Toyofuku M, Schild S, Kaparakis-Liaskos M, Eberl L. Composition and functions of bacterial membrane vesicles. Nat Rev Microbiol. 2023;21(7):415-430. doi: 10.1038/s41579-023-00875-5

 

  1. Melo-Marques I, Cardoso S M, Empadinhas N. Bacterial extracellular vesicles at the interface of gut microbiota and immunity. Gut Microbes. 2024;16(1):2396494. doi: 10.1080/19490976.2024.2396494

 

  1. Skotland T, Llorente A, Sandvig K. Lipids in Extracellular Vesicles: What Can Be Learned about Membrane Structure and Function?. Cold Spring Harb Perspect Biol. 2023;15(8):a041415. doi: 10.1101/cshperspect.a041415

 

  1. Liu J H, Chen C Y, Liu Z Z, et al. Extracellular vesicles from child gut microbiota enter into bone to preserve bone mass and strength. Adv Sci (Weinh). 2021;8(9):2004831. doi: 10.1002/advs.202004831

 

  1. Prados-Rosales R, Brown L, Casadevall A, Montalvo-Quirós S, Luque-Garcia JL. Isolation and identification of membrane vesicle-associated proteins in Gram-positive bacteria and mycobacteria. MethodsX. 2014;1:124-129. doi: 10.1016/j.mex.2014.08.001

 

  1. Vanaja S K, Russo A J, Behl B, et al. Bacterial outer membrane vesicles mediate cytosolic localization of LPS and caspase-11 activation. Cell. 2016;165(5):1106-1119. doi: 10.1016/j.cell.2016.04.015

 

  1. Lee E Y, Bang J Y, Park G W, et al. Global proteomic profiling of native outer membrane vesicles derived from Escherichia coli. Proteomics. 2007;7(17):3143-3153. doi: 10.1002/pmic.200700196

 

  1. Manabe T, Kato M, Ueno T, Kawasaki K. Flagella proteins contribute to the production of outer membrane vesicles from Escherichia coli W3110. Biochem Biophys Res Commun. 2013;441(1):151-156. doi: 10.1016/j.bbrc.2013.10.022

 

  1. Jang KS, Sweredoski MJ, Graham RL, Hess S, Clemons WM Jr. Comprehensive proteomic profiling of outer membrane vesicles from Campylobacter jejuni. J Proteomics. 2014;98:90-98. doi: 10.1016/j.jprot.2013.12.014

 

  1. Xie J, Li Q, Haesebrouck F, Van Hoecke L, Vandenbroucke RE. The tremendous biomedical potential of bacterial extracellular vesicles. Trends Biotechnol. 2022; 40(10): 1173-1194. doi: 10.1016/j.tibtech.2022.03.005

 

  1. Díaz-Garrido N, Badia J, Baldomà L. Microbiota-derived extracellular vesicles in interkingdom communication in the gut. J Extracell Vesicles. 2021;10(13):e12161. doi: 10.1002/jev2.12161

 

  1. Van Niel G, d’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19(4):213-228. doi: 10.1038/nrm.2017.125

 

  1. Zhao X, Wei Y, Bu Y, Ren X, Dong Z. Review on bacterial outer membrane vesicles: structure, vesicle formation, separation and biotechnological applications. Microb Cell Fact. 2025;24(1):27. doi: 10.1186/s12934-025-02653-9

 

  1. Clua-Ferré L, Suau R, Vañó-Segarra I, Ginés I, Serena C, Manyé J. Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles: A focus on inflammatory bowel disease. Clin Transl Med. 2024;14(11):e70075. doi: 10.1002/ctm2.70075

 

  1. Joshi B S, de Beer M A, Giepmans B N G, et al. Endocytosis of extracellular vesicles and release of their cargo from endosomes. ACS Nano. 2020;14(4):4444-4455. doi: 10.1021/acsnano.9b10033

 

  1. Zhu G, Yang F, Wei H, et al. 90K increased delivery efficiency of extracellular vesicles through mediating internalization. J Control Release. 2023;353:930-942. doi: 10.1016/j.jconrel.2022.12.034

 

  1. Geng Z, Sun T, Yuan L, Zhao Y. The existing evidence for the use of extracellular vesicles in the treatment of osteoporosis: a review. Int J Surg. 2025;111(5):3414-3429. doi: 10.1097/JS9.0000000000002339

 

  1. Haertinger M, Weiss T, Mann A, et al. Adipose stem cell-derived extracellular vesicles induce proliferation of Schwann cells via internalization. Cells. 2020;9(1):163. doi: 10.3390/cells9010163

 

  1. Yuan X, Sun L, Jeske R, et al. Engineering extracellular vesicles by three-dimensional dynamic culture of human mesenchymal stem cells. J Extracell Vesicles. 2022;11(6):e12235. doi: 10.1002/jev2.12235

 

  1. Carter K, Lee H J, Na K S, et al. Characterizing the impact of 2D and 3D culture conditions on the therapeutic effects of human mesenchymal stem cell secretome on corneal wound healing in vitro and ex vivo. Acta Biomater. 2019;99:247-257. doi: 10.1016/j.actbio.2019.09.022

 

  1. Sun L, Ji Y, Chi B, et al. A 3D culture system improves the yield of MSCs-derived extracellular vesicles and enhances their therapeutic efficacy for heart repair. Biomed Pharmacother. 2023;161:114557. doi: 10.1016/j.biopha.2023.114557

 

  1. Yang L, Zhai Y, Hao Y, Zhu Z, Cheng G. The Regulatory Functionality of Exosomes Derived from hUMSCs in 3D Culture for Alzheimer’s Disease Therapy. Small. 2020;16(3):e1906273. doi: 10.1002/smll.201906273

 

  1. Zinger A, Cvetkovic C, Sushnitha M, et al. Humanized biomimetic nanovesicles for neuron targeting. Adv Sci (Weinh). 2021;8(19):2101437. doi: 10.1002/advs.202101437

 

  1. Zhou J, Flores-Bellver M, Pan J, et al. Human retinal organoids release extracellular vesicles that regulate gene expression in target human retinal progenitor cells. Sci Rep. 2021;11(1):21128. doi: 10.1038/s41598-021-00542-w

 

  1. Arthur P, Kandoi S, Sun L, et al. Biophysical, Molecular and Proteomic Profiling of Human Retinal Organoid-Derived Exosomes. Pharm Res. 2023;40(4):801-816. doi: 10.1007/s11095-022-03350-7

 

  1. Alhasan L, Qi A, Al-Abboodi A, et al. Rapid enhancement of cellular spheroid assembly by acoustically driven microcentrifugation. ACS Biomater Sci Eng. 2016;2(6): 1013-22. doi: 10.1021/acsbiomaterials.6b00144.

 

  1. Rossi G, Manfrin A, Lutolf MP. Progress and potential in organoid research. Nat Rev Genet. 2018;19(11):671-87.doi: 10.1038/s41576-018-0051-9

 

  1. Villard A, Boursier J, Andriantsitohaina R. Microbiota-derived extracellular vesicles and metabolic syndrome. Acta Physiol (Oxf). 2021;231(4):e13600. doi: 10.1111/apha.13600

 

  1. Xing X, Han S, Cheng G, et al. Proteomic analysis of exosomes from adipose‐derived mesenchymal stem cells: a novel therapeutic strategy for tissue injury. Biomed Res Int. 2020;2020:6094562. doi: 10.1155/2020/6094562

 

  1. Schuster M, Braun FK, Chiang DM, et al. Extracellular vesicles secreted by 3D tumor organoids are enriched for immune regulatory signaling biomolecules compared to conventional 2D glioblastoma cell systems. Front Immunol. 2024;15:1388769. doi: 10.3389/fimmu.2024.1388769

 

  1. Proaño-Pérez E, Serrano-Candelas E, Guerrero M, et al. MITF regulates autophagy and extracellular vesicle cargo in gastrointestinal stromal tumors. Mol Biomed. 2025;6:92. doi: 10.1186/s43556-025-00329-9

 

  1. Upadhya R, Zingg W, Shetty S, Shetty AK. Astrocyte-derived extracellular vesicles: Neuroreparative properties and role in the pathogenesis of neurodegenerative disorders. J Control Release. 2020;323:225-239. doi: 10.1016/j.jconrel.2020.04.017

 

  1. Chansaenroj A, Adine C, Charoenlappanit S, et al. Magnetic bioassembly platforms towards the generation of extracellular vesicles from human salivary gland functional organoids for epithelial repair. Bioact Mater. 2022;18:151-163. doi: 10.1016/j.bioactmat.2022.02.007

 

  1. Roush S, Slack F J. The let-7 family of microRNAs. Trends Cell Biol. 2008;18(10):505-516. doi: 10.1016/j.tcb.2008.07.007

 

  1. Kwak S, Song C L, Lee J, et al. Development of pluripotent stem cell-derived epidermal organoids that generate effective extracellular vesicles in skin regeneration. Biomaterials. 2024;307:122522. doi: 10.1016/j.biomaterials.2024.122522

 

  1. Herrmann I K, Wood M J A, Fuhrmann G. Extracellular vesicles as a next-generation drug delivery platform. Nat Nanotechnol. 2021;16(7):748-759. doi: 10.1038/s41565-021-00931-2

 

  1. Zhang Y, Dou Y, Liu Y, et al. Advances in therapeutic applications of extracellular vesicles. Int J Nanomedicine. 2023;18:3285-3307. doi: 10.2147/ijn.s409588

 

  1. Elsharkasy O M, Nordin J Z, Hagey D W, et al. Extracellular vesicles as drug delivery systems: why and how? Adv Drug Deliv Rev. 2020;159:332-343. doi: 10.1016/j.addr.2020.04.004

 

  1. Liu H, Zhang H, Han Y, Hu Y, Geng Z, Su J. Bacterial extracellular vesicles-based therapeutic strategies for bone and soft tissue tumors therapy. Theranostics. 2022;12(15):6576-6594. doi: 10.7150/thno.78034

 

  1. Wu Y, Song P, Wang M, Liu H, Jing Y, Su J. Extracellular derivatives for bone metabolism. J Adv Res. 2024;66:329-347. doi: 10.1016/j.jare.2024.01.011

 

  1. Liu H, Su J. Organoid extracellular vesicle-based therapeutic strategies for bone therapy. Biomater Transl. 2023;4(4): 199-212. doi: 10.12336/biomatertransl.2023.04.002

 

  1. Nemati M, Singh B, Mir R A, et al. Plant-derived extracellular vesicles: a novel nanomedicine approach with advantages and challenges. Cell Commun Signal. 2022;20(1):69. doi: 10.1186/s12964-022-00889-1

 

  1. Rutter B D, Innes R W. Extracellular vesicles isolated from the leaf apoplast carry stress-response proteins. Plant Physiol. 2017;173(1):728-741. doi: 10.1104/pp.16.01253
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