REFERENCES
2. Hoang DM, Pham PT, Bach TQ, et al. Stem cell-based therapy for human diseases. Signal Transduct Target Ther. 2022;7:272.
3. Han Y, Yang J, Fang J, et al. The secretion profile of mesenchymal stem cells and potential applications in treating human diseases. Signal Transduct Target Ther. 2022;7:92.
4. Margiana R, Markov A, Zekiy AO, et al. Clinical application of mesenchymal stem cell in regenerative medicine: a narrative review. Stem Cell Res Ther. 2022;13:366.
5. Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008;8:726-36.
6. Zang L, Li Y, Hao H, et al. Efficacy of umbilical cord-derived mesenchymal stem cells in the treatment of type 2 diabetes assessed by retrospective continuous glucose monitoring. Stem Cells Transl Med. 2023;12:775-82.
7. Pagliuca FW, Millman JR, Gürtler M, et al. Generation of functional human pancreatic β cells in vitro. Cell. 2014;159:428-39.
8. Wang S, Du Y, Zhang B, et al. Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient. Cell. 2024;187:6152-64.e18.
9. Wu J, Li T, Guo M, et al.; Clinical Group. Treating a type 2 diabetic patient with impaired pancreatic islet function by personalized endoderm stem cell-derived islet tissue. Cell Discov. 2024;10:45.
10. Fischer UM, Harting MT, Jimenez F, et al. Pulmonary passage is a major obstacle for intravenous stem cell delivery: the pulmonary first-pass effect. Stem Cells Dev. 2009;18:683-92.
11. Mei R, Wan Z, Yang C, et al. Advances and clinical challenges of mesenchymal stem cell therapy. Front Immunol. 2024;15:1421854.
12. Ghittoni R, Patrussi L, Pirozzi K, et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med. 2005;11:367-8.
13. Liang X, Ding Y, Zhang Y, Tse HF, Lian Q. Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives. Cell Transplant. 2014;23:1045-59.
14. Xu G, Jin J, Fu Z, et al. Extracellular vesicle-based drug overview: research landscape, quality control and nonclinical evaluation strategies. Signal Transduct Target Ther. 2025;10:255.
15. Zhang K, Cheng K. Stem cell-derived exosome versus stem cell therapy. Nat Rev Bioeng. 2023;1:608-9.
16. Alpeeva EV, Ryabchenko AS, Vorotelyak EA. Characterization, preconditioning, safety, and other issues of MSC-derived EVs and secretome. Int J Mol Sci. 2026;27:1688.
17. Blanch RJ, Joseph IJ, Cockerham K. Traumatic optic neuropathy management: a systematic review. Eye. 2024;38:2312-8.
18. Williams PR, Benowitz LI, Goldberg JL, He Z. Axon regeneration in the mammalian optic nerve. Annu Rev Vis Sci. 2020;6:195-213.
19. An W, Zhang W, Qi J, et al. Mesenchymal stem cells and mesenchymal stem cell-derived exosomes: a promising strategy for treating retinal degenerative diseases. Mol Med. 2025;31:75.
20. Carney RP, Mizenko RR, Bozkurt BT, et al. Harnessing extracellular vesicle heterogeneity for diagnostic and therapeutic applications. Nat Nanotechnol. 2025;20:14-25.
21. Mizenko RR, Feaver M, Bozkurt BT, et al. A critical systematic review of extracellular vesicle clinical trials. J Extracell Vesicles. 2024;13:e12510.
22. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367:eaau6977.
23. EL Andaloussi S, Mäger I, Breakefield XO, Wood MJ. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013;12:347-57.
24. Welsh JA, Goberdhan DCI, O'Driscoll L, et al. ; MISEV Consortium. Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches. J Extracell Vesicles. 2024;13:e12404.
25. Dixson AC, Dawson TR, Di Vizio D, Weaver AM. Context-specific regulation of extracellular vesicle biogenesis and cargo selection. Nat Rev Mol Cell Biol. 2023;24:454-76.
26. Théry C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7:1535750.
27. Manno M, Bongiovanni A, Margolis L, Bergese P, Arosio P. The physico-chemical landscape of extracellular vesicles. Nat Rev Bioeng. 2025;3:68-82.
28. Rupert DLM, Claudio V, Lässer C, Bally M. Methods for the physical characterization and quantification of extracellular vesicles in biological samples. Biochim Biophys Acta Gen Subj. 2017;1861:3164-79.
29. Midekessa G, Godakumara K, Ord J, et al. Zeta potential of extracellular vesicles: toward understanding the attributes that determine colloidal stability. ACS Omega. 2020;5:16701-10.
30. Xia Y, Zhang J, Liu G, Wolfram J. Immunogenicity of extracellular vesicles. Adv Mater. 2024;36:e2403199.
31. Tang L, Yin Y, Cao Y, et al. Extracellular vesicles-derived hybrid nanoplatforms for amplified CD47 blockade-based cancer immunotherapy. Adv Mater. 2023;35:e2303835.
32. Buzas EI. The roles of extracellular vesicles in the immune system. Nat Rev Immunol. 2023;23:236-50.
33. Li M, Soder R, Abhyankar S, et al. WJMSC-derived small extracellular vesicle enhance T cell suppression through PD-L1. J Extracell Vesicles. 2021;10:e12067.
34. Vrablova V, Kosutova N, Blsakova A, et al. Glycosylation in extracellular vesicles: isolation, characterization, composition, analysis and clinical applications. Biotechnol Adv. 2023;67:108196.
35. Chen S, Iannotta D, O’Mara ML, Goncalves JP, Wolfram J. Extracellular vesicle lipids in cancer immunoevasion. Trends Cancer. 2023;9:883-6.
36. Liang X, Niu Z, Galli V, et al. Extracellular vesicles engineered to bind albumin demonstrate extended circulation time and lymph node accumulation in mouse models. J Extracell Vesicles. 2022;11:e12248.
37. Liu S, Lv K, Wang Y, et al. Improving the circulation time and renal therapeutic potency of extracellular vesicles using an endogenous ligand binding strategy. J Control Release. 2022;352:1009-23.
38. Nolte-’t Hoen E, Cremer T, Gallo RC, Margolis LB. Extracellular vesicles and viruses: are they close relatives? Proc Natl Acad Sci U S A 2016;113:9155-61.
39. Muskan M, Abeysinghe P, Cecchin R, Branscome H, Morris KV, Kashanchi F. Therapeutic potential of RNA-enriched extracellular vesicles: the next generation in RNA delivery via biogenic nanoparticles. Mol Ther. 2024;32:2939-49.
40. Morandi MI, Busko P, Ozer-Partuk E, et al. Extracellular vesicle fusion visualized by cryo-electron microscopy. PNAS Nexus. 2022;1:pgac156.
41. Papareddy P, Tapken I, Kroh K, et al. The role of extracellular vesicle fusion with target cells in triggering systemic inflammation. Nat Commun. 2024;15:1150.
42. L Ramos T, Sánchez-Abarca LI, Muntión S, et al. MSC surface markers (CD44, CD73, and CD90) can identify human MSC-derived extracellular vesicles by conventional flow cytometry. Cell Commun Signal. 2016;14:2.
43. Lee YJ, Shin KJ, Chae YC. Regulation of cargo selection in exosome biogenesis and its biomedical applications in cancer. Exp Mol Med. 2024;56:877-89.
44. Hu C, Yang J, Qi Z, et al. Heat shock proteins: biological functions, pathological roles, and therapeutic opportunities. MedComm. 2022;3:e161.
45. Chen J, Chen J, Cheng Y, et al. Mesenchymal stem cell-derived exosomes protect beta cells against hypoxia-induced apoptosis via miR-21 by alleviating ER stress and inhibiting p38 MAPK phosphorylation. Stem Cell Res Ther. 2020;11:97.
46. Wang Y, Jia J, Wang F, et al. Pre-metastatic niche: formation, characteristics and therapeutic implication. Signal Transduct Target Ther. 2024;9:236.
47. O'Brien K, Breyne K, Ughetto S, Laurent LC, Breakefield XO. RNA delivery by extracellular vesicles in mammalian cells and its applications. Nat Rev Mol Cell Biol. 2020;21:585-606.
48. Das A. Extracellular vesicles: tiny messengers for mighty RNA delivery. Biologics. 2024;4:88-104.
49. Ju C, Liu D. Exosomal microRNAs from mesenchymal stem cells: novel therapeutic effect in wound healing. Tissue Eng Regen Med. 2023;20:647-60.
50. Asgarpour K, Shojaei Z, Amiri F, et al. Exosomal microRNAs derived from mesenchymal stem cells: cell-to-cell messages. Cell Commun Signal. 2020;18:149.
51. Borcherding N, Brestoff JR. The power and potential of mitochondria transfer. Nature. 2023;623:283-91.
52. Liao Z, Tong B, Ke W, Yang C, Wu X, Lei M. Extracellular vesicles as carriers for mitochondria: biological functions and clinical applications. Mitochondrion. 2024;78:101935.
53. Liu D, Gao Y, Liu J, et al. Intercellular mitochondrial transfer as a means of tissue revitalization. Signal Transduct Target Ther. 2021;6:65.
54. Wang J, Xia J, Huang R, et al. Mesenchymal stem cell-derived extracellular vesicles alter disease outcomes via endorsement of macrophage polarization. Stem Cell Res Ther. 2020;11:424.
55. Zhao M, Liu S, Wang C, et al. Mesenchymal stem cell-derived extracellular vesicles attenuate mitochondrial damage and inflammation by stabilizing mitochondrial DNA. ACS Nano. 2021;15:1519-38.
56. Zorova LD, Kovalchuk SI, Popkov VA, et al. Do extracellular vesicles derived from mesenchymal stem cells contain functional mitochondria? Int J Mol Sci 2022;23:7408.
57. Hazan Ben-Menachem R, Lintzer D, Ziv T, et al. Mitochondrial-derived vesicles retain membrane potential and contain a functional ATP synthase. EMBO Rep. 2023;24:e56114.
58. Bao W, Xing H, Cao S, et al. Neutrophils restrain sepsis associated coagulopathy via extracellular vesicles carrying superoxide dismutase 2 in a murine model of lipopolysaccharide induced sepsis. Nat Commun. 2022;13:4583.
59. Phinney DG, Di Giuseppe M, Njah J, et al. Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs. Nat Commun. 2015;6:8472.
60. Byappanahalli AM, Noren Hooten N, Vannoy M, et al. Mitochondrial DNA and inflammatory proteins are higher in extracellular vesicles from frail individuals. Immun Ageing. 2023;20:6.
61. Cherian DS, Bhuvan T, Meagher L, Heng TSP. Biological considerations in scaling up therapeutic cell manufacturing. Front Pharmacol. 2020;11:654.
63. Chen W, Wu P, Jin C, Chen Y, Li C, Qian H. Advances in the application of extracellular vesicles derived from three-dimensional culture of stem cells. J Nanobiotechnology. 2024;22:215.
64. Casajuana Ester M, Day RM. Production and utility of extracellular vesicles with 3D culture methods. Pharmaceutics. 2023;15:663.
65. Liu D, Chen S, Win Naing M. A review of manufacturing capabilities of cell spheroid generation technologies and future development. Biotechnol Bioeng. 2021;118:542-54.
66. Jalilian E, Massoumi H, Bigit B, et al. Bone marrow mesenchymal stromal cells in a 3D system produce higher concentration of extracellular vesicles (EVs) with increased complexity and enhanced neuronal growth properties. Stem Cell Res Ther. 2022;13:425.
67. Xu C, Zhao J, Li Q, et al. Exosomes derived from three-dimensional cultured human umbilical cord mesenchymal stem cells ameliorate pulmonary fibrosis in a mouse silicosis model. Stem Cell Res Ther. 2020;11:503.
68. Zhang Y, Na T, Zhang K, et al. GMP-grade microcarrier and automated closed industrial scale cell production platform for culture of MSCs. J Tissue Eng Regen Med. 2022;16:934-44.
69. Zhang Q, Jeppesen DK, Higginbotham JN, Franklin JL, Coffey RJ. Comprehensive isolation of extracellular vesicles and nanoparticles. Nat Protoc. 2023;18:1462-87.
70. D’Acunzo P, Kim Y, Ungania JM, Pérez-González R, Goulbourne CN, Levy E. Isolation of mitochondria-derived mitovesicles and subpopulations of microvesicles and exosomes from brain tissues. Nat Protoc. 2022;17:2517-49.
71. Crescitelli R, Lässer C, Lötvall J. Isolation and characterization of extracellular vesicle subpopulations from tissues. Nat Protoc. 2021;16:1548-80.
72. Linares R, Tan S, Gounou C, Arraud N, Brisson AR. High-speed centrifugation induces aggregation of extracellular vesicles. J Extracell Vesicles. 2015;4:29509.
73. Chernyshev VS, Yashchenok A, Ivanov M, Silachev DN. Filtration-based technologies for isolation, purification and analysis of extracellular vesicles. Phys Chem Chem Phys. 2023;25:23344-57.
74. Romann P, Giller P, Sibilia A, et al. Co-current filtrate flow in TFF perfusion processes: Decoupling transmembrane pressure from crossflow to improve product sieving. Biotechnol Bioeng. 2024;121:640-54.
75. Malladi S, Coolbaugh MJ, Thomas C, et al. Design of a process development workflow and control strategy for single-pass tangential flow filtration and implementation for integrated and continuous biomanufacturing. J Membr Sci. 2023;677:121633.
76. Agrawal P, Wilkstein K, Guinn E, Mason M, Serrano Martinez CI, Saylae J. A review of tangential flow filtration: process development and applications in the pharmaceutical industry. Org Process Res Dev 2023;27:571-91.
77. Woo HK, Sunkara V, Park J, et al. Exodisc for rapid, size-selective, and efficient isolation and analysis of nanoscale extracellular vesicles from biological samples. ACS Nano. 2017;11:1360-70.
78. Kim K, Park J, Jung JH, et al. Cyclic tangential flow filtration system for isolation of extracellular vesicles. APL Bioeng. 2021;5:016103.
79. McNamara RP, Caro-Vegas CP, Costantini LM, et al. Large-scale, cross-flow based isolation of highly pure and endocytosis-competent extracellular vesicles. J Extracell Vesicles. 2018;7:1541396.
80. Li Z, Liu C, Cheng Y, et al. Cascaded microfluidic circuits for pulsatile filtration of extracellular vesicles from whole blood for early cancer diagnosis. Sci Adv. 2023;9:eade2819.
81. Guo J, Wu C, Lin X, et al. Establishment of a simplified dichotomic size-exclusion chromatography for isolating extracellular vesicles toward clinical applications. J Extracell Vesicles. 2021;10:e12145.
82. Chen P, Tang S, Gao H, et al. Wharton’s jelly mesenchymal stem cell-derived small extracellular vesicles as natural nanoparticles to attenuate cartilage injury via microRNA regulation. Int J Pharm. 2022;623:121952.
83. Diaz G, Bridges C, Lucas M, et al. Protein digestion, ultrafiltration, and size exclusion chromatography to optimize the isolation of exosomes from human blood plasma and serum. J Vis Exp. 2018;134:57467.
84. Böing AN, van der Pol E, Grootemaat AE, Coumans FA, Sturk A, Nieuwland R. Single-step isolation of extracellular vesicles by size-exclusion chromatography. J Extracell Vesicles. 2014;3:23430.
85. Pirolli NH, Reus LSC, Mamczarz Z, Khan S, Bentley WE, Jay SM. High performance anion exchange chromatography purification of probiotic bacterial extracellular vesicles enhances purity and anti-inflammatory efficacy. Biotechnol Bioeng. 2023;120:3368-80.
86. Fang SB, Zhang HY, Wang C, et al. Small extracellular vesicles derived from human mesenchymal stromal cells prevent group 2 innate lymphoid cell-dominant allergic airway inflammation through delivery of miR-146a-5p. J Extracell Vesicles. 2020;9:1723260.
87. Liu X, Zong Z, Liu X, et al. Stimuli-mediated specific isolation of exosomes from blood plasma for high-throughput profiling of cancer biomarkers. Small Methods. 2022;6:e2101234.
88. Li Q, Zhang Z, Wang F, et al. Reversible zwitterionic coordination enables rapid, high-yield, and high-purity isolation of extracellular vesicles from biofluids. Sci Adv. 2023;9:eadf4568.
89. Boriachek K, Masud MK, Palma C, et al. Avoiding pre-isolation step in exosome analysis: direct isolation and sensitive detection of exosomes using gold-loaded nanoporous ferric oxide nanozymes. Anal Chem. 2019;91:3827-34.
90. He F, Liu H, Guo X, Yin BC, Ye BC. Direct exosome quantification via bivalent-cholesterol-labeled DNA anchor for signal amplification. Anal Chem. 2017;89:12968-75.
91. Zhang K, Yue Y, Wu S, Liu W, Shi J, Zhang Z. Rapid capture and nondestructive release of extracellular vesicles using aptamer-based magnetic isolation. ACS Sens. 2019;4:1245-51.
92. Liu W, Wang X, Chen Y, et al. Distinct molecular properties and functions of small EV subpopulations isolated from human umbilical cord MSCs using tangential flow filtration combined with size exclusion chromatography. J Extracell Vesicles. 2025;14:e70029.
93. Iannotta D, A A, Lai A, et al. Chemically-induced lipoprotein breakdown for improved extracellular vesicle purification. Small. 2024;20:e2307240.
94. Keysberg C, Schneider H, Otte K. Production cell analysis and compound-based boosting of small extracellular vesicle secretion using a generic and scalable production platform. Biotechnol Bioeng. 2023;120:987-99.
95. Nguyen DDN, Vu DM, Vo N, et al. Skin rejuvenation and photoaging protection using adipose-derived stem cell extracellular vesicles loaded with exogenous cargos. Skin Res Technol. 2024;30:e13599.
96. Vo N, Tran C, Tran NHB, et al. A novel multi-stage enrichment workflow and comprehensive characterization for HEK293F-derived extracellular vesicles. J Extracell Vesicles. 2024;13:e12454.
97. Van Deun J, Jo A, Li H, et al. Integrated dual-mode chromatography to enrich extracellular vesicles from plasma. Adv Biosyst. 2020;4:e1900310.
98. Seo N, Nakamura J, Kaneda T, et al. Distinguishing functional exosomes and other extracellular vesicles as a nucleic acid cargo by the anion-exchange method. J Extracell Vesicles. 2022;11:e12205.
99. Tran HL, Zheng W, Issadore DA, et al. Extracellular vesicles for clinical diagnostics: from bulk measurements to single-vesicle analysis. ACS Nano. 2025;19:28021-109.
100. Hendrix A, Lippens L, Pinheiro C, et al. Extracellular vesicle analysis. Nat Rev Methods Primers. 2023;3:56.
101. Zhang J, Pan Y, She P, Rao L. From bench to bedside: the promise and roadblocks of extracellular vesicle therapeutics. Theranostics. 2026;16:5044-64.
102. Erdbrügger U, Lannigan J. Analytical challenges of extracellular vesicle detection: a comparison of different techniques. Cytometry A. 2016;89:123-34.
104. Jayakumar N, Ahluwalia BS. From superior contrast to super resolution label free optical microscopy. Npj Imaging. 2025;3:1.
105. Wong-Dilworth L, Rodilla-Ramirez C, Fox E, et al. STED imaging of endogenously tagged ARF GTPases reveals their distinct nanoscale localizations. J Cell Biol. 2023;222:e202205107.
106. Jeong D, Kim MJ, Park Y, et al. Visualizing extracellular vesicle biogenesis in gram-positive bacteria using super-resolution microscopy. BMC Biol. 2022;20:270.
107. Steen HB. Flow cytometer for measurement of the light scattering of viral and other submicroscopic particles. Cytometry A. 2004;57:94-9.
108. Tian Y, Ma L, Gong M, et al. Protein profiling and sizing of extracellular vesicles from colorectal cancer patients via flow cytometry. ACS Nano. 2018;12:671-80.
109. Wu L, Xue C, Tian Y, Hong X, Zhang M, Yan X. Development,application and prospects of nano-flow cytometry. J Xiamen Univ Nat Sci. 2021;60:178-90. (in Chinese).
110. Zhu S, Ma L, Wang S, et al. Light-scattering detection below the level of single fluorescent molecules for high-resolution characterization of functional nanoparticles. ACS Nano. 2014;8:10998-1006.
111. Zhang W, Tian Y, Hu X, et al. Light-scattering sizing of single submicron particles by high-sensitivity flow cytometry. Anal Chem. 2018;90:12768-75.
112. de Rond L, Coumans FAW, Nieuwland R, van Leeuwen TG, van der Pol E. Deriving extracellular vesicle size from scatter intensities measured by flow cytometry. Curr Protoc Cytom. 2018;86:e43.
113. Tian Y, Xue C, Zhang W, et al. Refractive index determination of individual viruses and small extracellular vesicles in aqueous media using nano-flow cytometry. Anal Chem. 2022;94:14299-307.
114. Liu H, Tian Y, Xue C, Niu Q, Chen C, Yan X. Analysis of extracellular vesicle DNA at the single-vesicle level by nano-flow cytometry. J Extracell Vesicles. 2022;11:e12206.
115. Chen C, Cai N, Niu Q, Tian Y, Hu Y, Yan X. Quantitative assessment of lipophilic membrane dye-based labelling of extracellular vesicles by nano-flow cytometry. J Extracell Vesicles. 2023;12:e12351.
116. Cai N, Zhan X, Chen Y, et al. Surface sialic acid detection of small extracellular vesicles at the single-particle level by nano-flow cytometry. Anal Chem. 2024;96:12718-28.
117. Ender F, Zamzow P, Bubnoff NV, Gieseler F. Detection and quantification of extracellular vesicles via FACS: membrane labeling matters! Int J Mol Sci 2019;21:291.
118. van der Pol E, van Gemert MJ, Sturk A, Nieuwland R, van Leeuwen TG. Single vs. swarm detection of microparticles and exosomes by flow cytometry. J Thromb Haemost. 2012;10:919-30.
119. Welsh JA, van der Pol E, Bettin BA, et al. Towards defining reference materials for measuring extracellular vesicle refractive index, epitope abundance, size and concentration. J Extracell Vesicles. 2020;9:1816641.
120. Jonas JB, Aung T, Bourne RR, Bron AM, Ritch R, Panda-Jonas S. Glaucoma. Lancet. 2017;390:2183-93.
121. Wang Y, Chen M, Tang Z, Gu P. Cell-based therapies for traumatic optic neuropathy: Recent advances, challenges, and perspectives. Neural Regen Res. 2026;21:1961-80.
123. Wallace DC, Lott MT. Leber hereditary optic neuropathy: exemplar of an mtDNA disease. Handb Exp Pharmacol. 2017;240:339-76.
124. Al-Zubidi N, Zhang J, Spitze A, Lee AG. Systemic corticosteroids in nonarteritic ischemic optic neuropathy. Indian J Ophthalmol. 2014;62:1022-4.
125. Aneesh A, Liu A, Moss HE, et al. Emerging concepts in the treatment of optic neuritis: mesenchymal stem cell-derived extracellular vesicles. Stem Cell Res Ther. 2021;12:594.
126. Wu KY, Ahmad H, Lin G, Carbonneau M, Tran SD. Mesenchymal stem cell-derived exosomes in ophthalmology: a comprehensive review. Pharmaceutics. 2023;15:1167.
127. Su Y, Chen M, Xu W, Gu P, Fan X. Advances in extracellular-vesicles-based diagnostic and therapeutic approaches for ocular diseases. ACS Nano. 2024;18:22793-828.
128. Herman S, Fishel I, Offen D. Intranasal delivery of mesenchymal stem cells-derived extracellular vesicles for the treatment of neurological diseases. Stem Cells. 2021;39:1589-600.
129. Ye X, Liu Y, Chen C, et al. A novel function and mechanism of ischemia-induced retinal astrocyte-derived exosomes for RGC apoptosis of ischemic retinopathy. Mol Ther Nucleic Acids. 2024;35:102209.
130. Zhu S, Chen L, Wang M, et al. Schwann cell-derived extracellular vesicles as a potential therapy for retinal ganglion cell degeneration. J Control Release. 2023;363:641-56.
131. Cui Y, Liu C, Huang L, Chen J, Xu N. Protective effects of intravitreal administration of mesenchymal stem cell-derived exosomes in an experimental model of optic nerve injury. Exp Cell Res. 2021;407:112792.
132. Pan D, Chang X, Xu M, et al. UMSC-derived exosomes promote retinal ganglion cells survival in a rat model of optic nerve crush. J Chem Neuroanat. 2019;96:134-9.
133. Yu Z, Wen Y, Jiang N, et al. TNF-α stimulation enhances the neuroprotective effects of gingival MSCs derived exosomes in retinal ischemia-reperfusion injury via the MEG3/miR-21a-5p axis. Biomaterials. 2022;284:121484.
134. Dan QQ, Chen L, Shi LL, Zhou X, Wang TH, Liu H. Urine-derived mesenchymal stem cells-derived exosomes enhances survival and proliferation of aging retinal ganglion cells. BMC Mol Cell Biol. 2023;24:8.
135. Mead B, Ahmed Z, Tomarev S. Mesenchymal stem cell-derived small extracellular vesicles promote neuroprotection in a genetic DBA/2J mouse model of glaucoma. Invest Ophthalmol Vis Sci. 2018;59:5473-80.
136. Mead B, Amaral J, Tomarev S. Mesenchymal stem cell-derived small extracellular vesicles promote neuroprotection in rodent models of glaucoma. Invest Ophthalmol Vis Sci. 2018;59:702-14.
137. You T, Yang Y, A L, et al. IFNγ preconditioning improves neuroprotection of MSC-derived vesicles on injured retinal ganglion cells by suppressing microglia activation via miRNA-dependent ribosome activity. Extracell Vesicles Circ Nucl Acids. 2025;6:87-111.
138. Chen L, Yu Z, Zhu S, et al. Astrocyte-derived extracellular vesicles alleviate optic nerve injury through remodeling of retinal microenvironmental homeostasis. Invest Ophthalmol Vis Sci. 2025;66:16.
139. Ji S, Peng Y, Liu J, Xu P, Tang S. Human adipose tissue-derived stem cell extracellular vesicles attenuate ocular hypertension-induced retinal ganglion cell damage by inhibiting microglia- TLR4/MAPK/NF-κB proinflammatory cascade signaling. Acta Neuropathol Commun. 2024;12:44.
140. Mathew B, Acha LG, Torres LA, et al. MicroRNA-based engineering of mesenchymal stem cell extracellular vesicles for treatment of retinal ischemic disorders: Engineered extracellular vesiclesand retinal ischemia. Acta Biomater. 2023;158:782-97.
141. Wang Y, Yu HY, Yi ZJ, et al. Super mitochondria-enriched extracellular vesicles enable enhanced mitochondria transfer. Nat Commun. 2025;16:9448.
142. Kim M, Kim JY, Rhim WK, et al. Extracellular vesicle encapsulated nicotinamide delivered via a trans-scleral route provides retinal ganglion cell neuroprotection. Acta Neuropathol Commun. 2024;12:65.
143. Mead B, Tomarev S. Bone marrow-derived mesenchymal stem cells-derived exosomes promote survival of retinal ganglion cells through miRNA-dependent mechanisms. Stem Cells Transl Med. 2017;6:1273-85.
144. Seyedrazizadeh SZ, Poosti S, Nazari A, et al. Extracellular vesicles derived from human ES-MSCs protect retinal ganglion cells and preserve retinal function in a rodent model of optic nerve injury. Stem Cell Res Ther. 2020;11:203.
145. Sang X, Tang L, Zhao L, et al. Umbilical cord mesenchymal stem cell-derived exosomes promote axon regeneration during optic nerve injury through microRNA-dependent mTORC1 signalling. Clin Transl Med. 2023;13:e1319.
146. Jeppesen DK, Fenix AM, Franklin JL, et al. Reassessment of exosome composition. Cell. 2019;177:428-45.e18.
147. Falavarjani KG, Nguyen QD. Adverse events and complications associated with intravitreal injection of anti-VEGF agents: a review of literature. Eye. 2013;27:787-94.
148. Thareja A, Hughes H, Alvarez-Lorenzo C, Hakkarainen JJ, Ahmed Z. Penetration enhancers for topical drug delivery to the ocular posterior segment-a systematic review. Pharmaceutics. 2021;13:276.
149. Gotoh S, Kawabori M, Fujimura M. Intranasal administration of stem cell-derived exosomes for central nervous system diseases. Neural Regen Res. 2024;19:1249-55.
150. Sánchez SV, Otavalo GN, Gazeau F, Silva AKA, Morales JO. Intranasal delivery of extracellular vesicles: a promising new approach for treating neurological and respiratory disorders. J Control Release. 2025;379:489-523.
151. Herrmann IK, Wood MJA, Fuhrmann G. Extracellular vesicles as a next-generation drug delivery platform. Nat Nanotechnol. 2021;16:748-59.
152. A L, Qu L, He J, et al. Exosomes derived from IFNγ-stimulated mesenchymal stem cells protect photoreceptors in RCS rats by restoring immune homeostasis through tsRNAs. Cell Commun Signal. 2024;22:543.
153. Wu J, Wu J, Xiang W, et al. Engineering exosomes derived from TNF-α preconditioned IPFP-MSCs enhance both yield and therapeutic efficacy for osteoarthritis. J Nanobiotechnology. 2024;22:555.
154. Li J, Wang T, Hou X, et al. Extracellular vesicles: opening up a new perspective for the diagnosis and treatment of mitochondrial dysfunction. J Nanobiotechnology. 2024;22:487.
155. Yang W, Wang X, Zheng D, et al. Catalytic neural stem cell exosomes for multi-stage targeting and synergistical therapy of retinal ischemia-reperfusion injury. Cell Rep Med. 2025;6:102052.
156. Zhang H, Lyden D. Asymmetric-flow field-flow fractionation technology for exomere and small extracellular vesicle separation and characterization. Nat Protoc. 2019;14:1027-53.
157. Gao Z, Hutchins Z, Li Z, Zhong W. Offline coupling of asymmetrical flow field-flow fractionation and capillary electrophoresis for separation of extracellular vesicles. Anal Chem. 2022;94:14083-91.
158. Zimmerman AJ, de Oliveira GP Jr, Su X, et al. Multimode chromatography-based techniques for high purity isolation of extracellular vesicles from human blood plasma. J Extracell Biol. 2024;3:e147.
159. Haraszti RA, Miller R, Stoppato M, et al. Exosomes produced from 3D cultures of MSCs by tangential flow filtration show higher yield and improved activity. Mol Ther. 2018;26:2838-47.
160. Lee JH, Ha DH, Go HK, et al. Reproducible large-scale isolation of exosomes from adipose tissue-derived mesenchymal stem/stromal cells and their application in acute kidney injury. Int J Mol Sci. 2020;21:4774.
161. Tian M, Ticer T, Wang Q, et al. Adipose-derived biogenic nanoparticles for suppression of inflammation. Small. 2020;16:e1904064.
162. Wolf M, Poupardin RW, Ebner-Peking P, et al. A functional corona around extracellular vesicles enhances angiogenesis, skin regeneration and immunomodulation. J Extracell Vesicles. 2022;11:e12207.
163. Zeng X, Yi X, Chen L, et al. Characterization and bioassays of extracellular vesicles extracted by tangential flow filtration. Regen Med. 2022;17:141-54.
