[Home ] [Archive]   [ فارسی ]  
:: Main :: About :: Current Issue :: Archive :: Search :: Submit :: Contact ::
Main Menu
Home::
Journal Information::
Indexing Sources::
Guide for Authors::
Online Submission::
Ethics::
Articles archive::
For Reviewers::
Contact us::
AI::
::
Basic and Clinical Biochemistry and Nutrition
..
DOAJ
..
CINAHL
..
EBSCO
..
IMEMR
..
ISC
..
Search in website

Advanced Search
..
Receive site information
Enter your Email in the following box to receive the site news and information.
..
enamad
..
:: Volume 30, Issue 1 (Bimonthly 2026) ::
Feyz Med Sci J 2026, 30(1): 112-128 Back to browse issues page
The Role of Exosomes in Ischemic Stroke: Emerging Diagnostic and Therapeutic Approaches and Challenges in Clinical Translation
Zeinab Vahidinia * , Elahe Seyed Hosseini
Anatomical Sciences Research Center, Institute of Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran , vahidinia-z@kaums.ac.ir
Abstract:   (298 Views)
Background and Aim: Ischemic stroke is one of the leading causes of mortality and long-term neurological disability worldwide, with high incidence, recurrence rates, and substantial disabling consequences. Despite significant scientific advances, diagnostic and therapeutic options in the acute phase -particularly in ischemia-reperfusion injury- remain limited, and many neuroprotective agents that demonstrated preclinical efficacy have failed in clinical trials. This narrative review aimed to elucidate the role of exosomes in the pathophysiology, diagnosis, and treatment of ischemic stroke, as well as to discuss the challenges and future perspectives regarding their clinical translation.
Methods: This study was conducted as a narrative review by systematically examining relevant literature on exosomes and ischemic stroke and synthesizing the available evidence.
Results: Exosomes are nanoscale extracellular vesicles secreted by various cell types and are recognized as key mediators of intercellular communication within the central nervous system. Due to their ability to cross the blood–brain barrier, low immunogenicity and toxicity, and capacity to transport bioactive molecules such as miRNAs, proteins, and lipids, exosomes play a critical role in both pathophysiological and reparative processes following ischemic stroke. Evidence suggests that exosomes may serve as non-invasive biomarkers for assessing injury severity and predicting prognosis. Furthermore, they exhibit neuroprotective and regenerative properties by modulating inflammation, apoptosis, autophagy, neurogenesis, and angiogenesis after ischemic injury.
Conclusion: Exosomes represent a promising novel tool in neurobiology and regenerative medicine with significant potential for the diagnosis, prognosis, and treatment of ischemic stroke. However, challenges including standardization of isolation techniques, immunogenicity concerns, targeted delivery, and scalability of production remain major barriers to their clinical translation.
Keywords: Ischemic stroke, Exosomes, miRNA, Inflammation, Apoptosis, Autophagy, Neurogenesis, Angiogenesis
Full-Text [PDF 518 kb]   (27 Downloads)    
Type of Study: Review | Subject: medicine, paraclinic
Received: 2025/08/3 | Revised: 2026/04/19 | Accepted: 2025/12/30 | Published: 2026/03/15
References
1. Khassafi N, Tameh AA, Mirzaei H, Rafat A, Barati S, Khassafi N, et al. Crosstalk between Nrf2 signaling pathway and inflammation in ischemic stroke: Mechanisms of action and therapeutic implications. Exp Neurol. 2023; 369:114655. doi:10.1016/j.expneurol.2023.114655 PMid:38110142
2. Nejati M, Tameh AA, Vahidinia Z, Atlasi MA. Mesenchymal stem cells improve ischemic stroke injury by anti-inflammatory properties in rat model of middle cerebral artery occlusion. Iran Red Crescent Med J. 2018;20(1). doi:10.5812/ircmj.55085
3. Strain WD, Elyas S, Wedge N, Mounce L, Henley W, James M, et al. Evaluation of microalbuminuria as a prognostic indicator after a TIA or minor stroke in an outpatient setting: the prognostic role of microalbuminuria in TIA evolution (ProMOTE) study. BMJ Open. 2021;11(9):e043253. doi:10.1136/bmjopen-2020-043253 PMid:34489262 PMCid:PMC8422314
4. Hankey GJ. Stroke. Lancet. 2017; 389(10069):641-654. doi:10.1016/S0140-6736(16)30962-X PMid:27637676 PMCid:PMC12123089
5. Samaniego EA, Roa JA, Limaye K, Adams HP Jr. Mechanical thrombectomy: emerging technologies and techniques. J Stroke Cerebrovasc Dis. 2018; 27(10):2555-2571. doi:10.1016/j.jstrokecerebrovasdis.2018.05.025 PMid:29960666
6. Svendsen SP, Svendsen CN. Cell therapy for neurological disorders. Nat Med. 2024;30(10):2756-2770. doi:10.1038/s41591-024-03281-3 PMid:39407034
7. Detante O, Legris L, Moisan A, Rome C. Cell Therapy and Functional Recovery of Stroke. Neuroscience. 2024;550:79-88. doi:10.1016/j.neuroscience.2023.11.027 PMid:38013148
8. Unsworth D, Mathias J, Dorstyn D, Koblar S. Are patient educational resources effective at deterring stroke survivors from considering experimental stem cell treatments? A randomized controlled trial. Patient Educ Couns. 2020;103(7):1373-1381. doi:10.1016/j.pec.2020.02.012 PMid:32081514
9. Cunningham NA, Abhyankar P, Cowie J, Galinsky J, Methven K. Regenerative medicine: stroke survivor and carer views and motivations towards a proposed stem cell clinical trial using placebo neurosurgery. Health Expect. 2018; 21(1): 367-378. doi:10.1111/hex.12632 PMid:29024214 PMCid:PMC5750757
10. George MJ, Prabhakara K, Toledano-Furman NE, Wang YW, Gill BS, Wade CE, et al. Clinical cellular therapeutics accelerate clot formation. Stem Cells Transl Med. 2018;7(10):731-739. doi:10.1002/sctm.18-0015 PMid:30070065 PMCid:PMC6186273
11. Lukomska B, Stanaszek L, Zuba-Surma E, Legosz P, Sarzynska S, Drela K. Challenges and controversies in human mesenchymal stem cell therapy. Stem Cells Int. 2019;2019:9628536. doi:10.1155/2019/9628536 PMid:31093291 PMCid:PMC6481040
12. Cai Y, Liu W, Lian L, Xu Y, Bai X, Xu S, et al. Stroke treatment: Is exosome therapy superior to stem cell therapy? Biochimie. 2020;179:190-204. doi:10.1016/j.biochi.2020.09.025 PMid:33010339
13. Yang J, Zhang X, Chen X, Wang L, Yang G. Exosome mediated delivery of miR-124 promotes neurogenesis after ischemia. Mol Ther Nucleic Acids. 2017;7:278-287. doi:10.1016/j.omtn.2017.04.010 PMid:28624203 PMCid:PMC5415550
14. Hong SB, Yang H, Manaenko A, Lu J, Mei Q, Hu Q. Potential of exosomes for the treatment of stroke. Cell Transplant. 2019;28(6):662-670. doi:10.1177/0963689718816990 PMid:30520322 PMCid:PMC6686440
15. Vahidinia Z, Azami Tameh A, Barati S, Izadpanah M, Seyed Hosseini E. Nrf2 activation: a key mechanism in stem cell exosomes-mediated therapies. Cell Mol Biol Lett. 2024;29(1):30. doi:10.1186/s11658-024-00551-3 PMid:38431569 PMCid:PMC10909300
16. Hessvik NP, Llorente A. Current knowledge on exosome biogenesis and release. Cell Mol Life Sci. 2018; 75(2):193-208. doi:10.1007/s00018-017-2595-9 PMid:28733901 PMCid:PMC8492061
17. Yu B, Zhang X, Li X. Exosomes derived from mesenchymal stem cells. Int J Mol Sci. 2014; 15(3): 4142-57. doi:10.3390/ijms15034142 PMid:24608926 PMCid:PMC3975389
18. Krylova SV, Feng D. The Machinery of Exosomes: Biogenesis, Release, and Uptake. Int J Mol Sci. 2023;24(2). doi:10.3390/ijms24021337 PMid:36674857 PMCid:PMC9865891
19. Ueno Y, Hira K, Miyamoto N, Kijima C, Inaba T, Hattori N. Pleiotropic Effects of Exosomes as a Therapy for Stroke Recovery. Int J Mol Sci. 2020; 21(18). doi:10.3390/ijms21186894 PMid:32962207 PMCid:PMC7555640
20. Forró T, Bajkó Z, Bălașa A, Bălașa R. Dysfunction of the Neurovascular Unit in Ischemic Stroke: Highlights on microRNAs and Exosomes as Potential Biomarkers and Therapy. Int J Mol Sci. 2021; 22(11). doi:10.3390/ijms22115621 PMid:34070696 PMCid:PMC8198979
21. Shahjin F, Chand S, Yelamanchili SV. Extracellular vesicles as drug delivery vehicles to the central nervous system. J Neuroimmune Pharmacol. 2020; 15:443-458. doi:10.1007/s11481-019-09875-w PMid:31485884
22. He R, Jiang Y, Shi Y, Liang J, Zhao L. Curcumin-laden exosomes target ischemic brain tissue and alleviate cerebral ischemia-reperfusion injury by inhibiting ROS-mediated mitochondrial apoptosis. Mater Sci Eng C Mater Biol Appl. 2020; 117:111314. doi:10.1016/j.msec.2020.111314 PMid:32919674
23. Liu Y, Fu N, Su J, Wang X, Li X. Rapid Enkephalin Delivery Using Exosomes to Promote Neurons Recovery in Ischemic Stroke by Inhibiting Neuronal p53/Caspase 3. Biomed Res Int. 2019; 2019:4273290. doi:10.1155/2019/4273290 PMid:30949500 PMCid:PMC6425296
24. He C, Hua W, Liu J, Fan L, Wang H, Sun G. Exosomes derived from endoplasmic reticulum-stressed liver cancer cells enhance the expression of cytokines in macrophages via the STAT3 signaling pathway. Oncol Lett. 2020;20(1):589-600. doi:10.3892/ol.2020.11609 PMid:32565984 PMCid:PMC7285763
25. Cheng L, Zhang K, Wu S, Cui M, Xu T. Focus on mesenchymal stem cell derived exosomes: opportunities and challenges in cell free therapy. Stem Cells Int. 2017;2017:6305295. doi:10.1155/2017/6305295 PMid:29410682 PMCid:PMC5749272
26. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020; 367(6478):eaau6977. doi:10.1126/science.aau6977 PMid:32029601 PMCid:PMC7717626
27. Piper RC, Katzmann DJ. Biogenesis and function of multivesicular bodies. Annu Rev Cell Dev Biol. 2007;23(1):519-547. doi:10.1146/annurev.cellbio.23.090506.123319 PMid:17506697 PMCid:PMC2911632
28. Luzio JP, Gray SR, Bright NA. Endosome-lysosome fusion. Portland Press Ltd; 2010. doi:10.1042/BST0381413 PMid:21118098
29. Théry C. Exosomes: secreted vesicles and intercellular communications. F1000 Biol Rep. 2011; 3:15. doi:10.3410/B3-15 PMid:21876726 PMCid:PMC3155154
30. Sinha S, Hoshino D, Hong NH, Kirkbride KC, Grega-Larson NE, Seiki M, et al. Cortactin promotes exosome secretion by controlling branched actin dynamics. J Cell Biol. 2016;214(2):197-213. doi:10.1083/jcb.201601025 PMid:27402952 PMCid:PMC4949450
31. Baietti MF, Zhang Z, Mortier E, Melchior A, Degeest G, Geeraerts A, et al. Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat Cell Biol. 2012; 14(7):677-685. doi:10.1038/ncb2502 PMid:22660413
32. Batista BS, Eng WS, Pilobello KT, Hendricks-Muñoz KD, Mahal LK. Identification of a conserved glycan signature for microvesicles. J Proteome Res. 2011; 10 (10):4624-4633. doi:10.1021/pr200434y PMid:21859146 PMCid:PMC3443565
33. Keerthikumar S, Gangoda L, Liem M, Fonseka P, Atukorala I, Ozcitti C, et al. Proteogenomic analysis reveals exosomes are more oncogenic than ectosomes. Oncotarget. 2015;6(17):15375. doi:10.18632/oncotarget.3801 PMid:25944692 PMCid:PMC4558158
34. Kalra H, Drummen GP, Mathivanan S. Focus on extracellular vesicles: introducing the next small big thing. Int J Mol Sci. 2016;17(2):170. doi:10.3390/ijms17020170 PMid:26861301 PMCid:PMC4783904
35. Geng T, Song ZY, Xing JX, Wang BX, Dai SP, Xu ZS. Exosome derived from coronary serum of patients with myocardial infarction promotes angiogenesis through the miRNA-143/IGF-IR pathway. Int J Nanomedicine. 2020;15:2647-2658. doi:10.2147/IJN.S242908 PMid:32368046 PMCid:PMC7183550
36. Xin H, Liu Z, Buller B, Li Y, Golembieski W, Gan X, et al. MiR-17-92 enriched exosomes derived from multipotent mesenchymal stromal cells enhance axon-myelin remodeling and motor electrophysiological recovery after stroke. J Cereb Blood Flow Metab. 2021; 41(5):1131-1144. doi:10.1177/0271678X20950489 PMid:32811262 PMCid:PMC8054728
37. Ling X, Zhang G, Xia Y, Zhu Q, Zhang J, Li Q, et al. Exosomes from human urine derived stem cells enhanced neurogenesis via miR 26a/HDAC6 axis after ischaemic stroke. J Cell Mol Med. 2020; 24(1): 640-654. doi:10.1111/jcmm.14774 PMid:31667951 PMCid:PMC6933407
38. Xin H, Katakowski M, Wang F, Qian JY, Liu XS, Ali MM, et al. MicroRNA-17-92 cluster in exosomes enhance neuroplasticity and functional recovery after stroke in rats. Stroke. 2017;48(3):747-753. doi:10.1161/STROKEAHA.116.015204 PMid:28232590 PMCid:PMC5330787
39. Xin H, Wang F, Li Y, Lu QE, Cheung WL, Zhang Y, et al. Secondary release of exosomes from astrocytes contributes to the increase in neural plasticity and improvement of functional recovery after stroke in rats treated with exosomes harvested from microRNA 133b-overexpressing multipotent mesenchymal stromal cells. Cell Transplant. 2017; 26(2): 243-257. doi:10.3727/096368916X693031 PMid:27677799 PMCid:PMC5303172
40. Chen HS, Tong HS, Zhao Y, Hong CY, Bin JP, Su L. Differential expression pattern of exosome long non-coding RNAs (lncRNAs) and MicroRNAs (miRNAs) in vascular endothelial cells under heat stroke. Med Sci Monit. 2018;24:7965. doi:10.12659/MSM.909983 PMid:30399613 PMCid:PMC6234752
41. Xin H, Li Y, Cui Y, Yang JJ, Zhang ZG, Chopp M. Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats. J Cereb Blood Flow Metab. 2013;33(11):1711-1715. doi:10.1038/jcbfm.2013.152 PMid:23963371 PMCid:PMC3824189
42. Li P, Kaslan M, Lee SH, Yao J, Gao Z. Progress in exosome isolation techniques. Theranostics. 2017; 7(3):789. doi:10.7150/thno.18133 PMid:28255367 PMCid:PMC5327650
43. Bobrie A, Colombo M, Krumeich S, Raposo G, Théry C. Diverse subpopulations of vesicles secreted by different intracellular mechanisms are present in exosome preparations obtained by differential ultracentrifugation. J Extracell Vesicles. 2012; 1(1):18397. doi:10.3402/jev.v1i0.18397 PMid:24009879 PMCid:PMC3760636
44. Rider MA, Hurwitz SN, Meckes DG Jr. ExtraPEG: a polyethylene glycol-based method for enrichment of extracellular vesicles. Sci Rep. 2016; 6(1):23978. doi:10.1038/srep23978 PMid:27068479 PMCid:PMC4828635
45. Han Y, Jia L, Zheng Y, Li W. Salivary exosomes: emerging roles in systemic disease. Int J Biol Sci. 2018;14(6):633. doi:10.7150/ijbs.25018 PMid:29904278 PMCid:PMC6001649
46. Sokolova V, Ludwig AK, Hornung S, Rotan O, Horn PA, Epple M, et al. Characterisation of exosomes derived from human cells by nanoparticle tracking analysis and scanning electron microscopy. Colloids Surf B Biointerfaces. 2011;87(1):146-150. doi:10.1016/j.colsurfb.2011.05.013 PMid:21640565
47. Mathivanan S, Lim JW, Tauro BJ, Ji H, Moritz RL, Simpson RJ. Proteomics analysis of A33 immunoaffinity-purified exosomes released from the human colon tumor cell line LIM1215 reveals a tissue-specific protein signature. Mol Cell Proteomics. 2010;9(2):197-208. doi:10.1074/mcp.M900152-MCP200 PMid:19837982 PMCid:PMC2830834
48. Lee K, Shao H, Weissleder R, Lee H. Acoustic purification of extracellular microvesicles. ACS Nano. 2015;9(3):2321-2327. doi:10.1021/nn506538f PMid:25672598 PMCid:PMC4373978
49. Xu Y, Hu Y, Xu S, Liu F, Gao Y. Exosomal microRNAs as potential biomarkers and therapeutic agents for acute ischemic stroke: new expectations. Front Neurol. 2022;12:747380. doi:10.3389/fneur.2021.747380 PMid:35173663 PMCid:PMC8842672
50. Makris K, Haliassos A, Chondrogianni M, Tsivgoulis G. Blood biomarkers in ischemic stroke: potential role and challenges in clinical practice and research. Crit Rev Clin Lab Sci. 2018;55(5):294-328. doi:10.1080/10408363.2018.1461190 PMid:29668333
51. Osier N, Motamedi V, Edwards K, Puccio A, Diaz-Arrastia R, Kenney K, et al. Exosomes in acquired neurological disorders: new insights into pathophysiology and treatment. Mol Neurobiol. 2018;55:9280-9293. doi:10.1007/s12035-018-1054-4 PMid:29663285
52. Kanhai DA, de Kleijn DP, Kappelle LJ, Uiterwaal CS, van der Graaf Y, Pasterkamp G, et al. Extracellular vesicle protein levels are related to brain atrophy and cerebral white matter lesions in patients with manifest vascular disease: the SMART-MR study. BMJ Open. 2014;4(1):e003824. doi:10.1136/bmjopen-2013-003824 PMid:24430876 PMCid:PMC3902438
53. Datta A, Chen CP, Sze SK. Discovery of prognostic biomarker candidates of lacunar infarction by quantitative proteomics of microvesicles enriched plasma. PLoS One. 2014; 9(4):e94663. doi:10.1371/journal.pone.0094663 PMid:24752076 PMCid:PMC3994162
54. Cipollone F, Felicioni L, Sarzani R, Ucchino S, Spigonardo F, Mandolini C, et al. A unique microRNA signature associated with plaque instability in humans. Stroke. 2011;42(9):2556-2563. doi:10.1161/STROKEAHA.110.597575 PMid:21817153
55. Ji Q, Ji Y, Peng J, Zhou X, Chen X, Zhao H, et al. Increased brain-specific MiR-9 and MiR-124 in the serum exosomes of acute ischemic stroke patients. PLoS One. 2016;11(9):e0163645. doi:10.1371/journal.pone.0163645 PMid:27661079 PMCid:PMC5035015
56. Chen Y, Song Y, Huang J, Qu M, Zhang Y, Geng J, et al. Increased circulating exosomal miRNA-223 is associated with acute ischemic stroke. Front Neurol. 2017; 8:57. doi:10.3389/fneur.2017.00057 PMid:28289400 PMCid:PMC5326773
57. Zhou J, Chen L, Chen B, Huang S, Zeng C, Wu H, et al. Increased serum exosomal miR-134 expression in the acute ischemic stroke patients. BMC Neurol. 2018;18:1-9. doi:10.1186/s12883-018-1196-z PMid:30514242 PMCid:PMC6278025
58. Jia L, Hao F, Wang W, Qu Y. Circulating miR 145 is associated with plasma high sensitivity C reactive protein in acute ischemic stroke patients. Cell Biochem Funct. 2015;33(5):314-319. doi:10.1002/cbf.3116 PMid:26096228
59. Shan Y, Hu J, Lv H, Cui X, Di W. miR-221 exerts neuroprotective effects in ischemic stroke by inhibiting the proinflammatory response. J Stroke Cerebrovasc Dis. 2021;30(2):105489. doi:10.1016/j.jstrokecerebrovasdis.2020.105489 PMid:33276305
60. Dolz S, Górriz D, Tembl JI, Sánchez D, Fortea G, Parkhutik V, et al. Circulating microRNAs as novel biomarkers of stenosis progression in asymptomatic carotid stenosis. Stroke. 2017; 48(1): 10-16. doi:10.1161/STROKEAHA.116.013650 PMid:27899750
61. Otero-Ortega L, Alonso-López E, Pérez-Mato M, Laso-García F, Gómez-de Frutos MC, Diekhorst L, et al. Circulating extracellular vesicle proteins and microRNA profiles in subcortical and cortical-subcortical ischaemic stroke. Biomedicines. 2021; 9(7):786. doi:10.3390/biomedicines9070786 PMid:34356850 PMCid:PMC8301391
62. Wang W, Li DB, Li RY, Zhou X, Yu DJ, Lan XY, et al. Diagnosis of hyperacute and acute ischaemic stroke: the potential utility of exosomal MicroRNA-21-5p and MicroRNA-30a-5p. Cerebrovasc Dis. 2018; 45(5-6):204-212. doi:10.1159/000488365 PMid:29627835
63. Li DB, Liu JL, Wang W, Li RY, Yu DJ, Lan XY, et al. Plasma exosomal miR-422a and miR-125b-2-3p serve as biomarkers for ischemic stroke. Curr Neurovasc Res. 2017;14(4):330-337. doi:10.2174/1567202614666171005153434 PMid:28982331
64. Tian T, Zhang HX, He CP, Fan S, Zhu YL, Qi C, et al. Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy. Biomaterials. 2018; 150:137-149. doi:10.1016/j.biomaterials.2017.10.012 PMid:29040874
65. Huang M, Hong Z, Xiao C, Li L, Chen L, Cheng S, et al. Effects of exosomes on neurological function recovery for ischemic stroke in pre-clinical studies: a meta-analysis. Front Cell Neurosci. 2020; 14: 593130. doi:10.3389/fncel.2020.593130 PMid:33324166 PMCid:PMC7726242
66. Pei X, Li Y, Zhu L, Zhou Z. Astrocyte-derived exosomes suppress autophagy and ameliorate neuronal damage in experimental ischemic stroke. Exp Cell Res. 2019;382(2):111474. doi:10.1016/j.yexcr.2019.06.019 PMid:31229506
67. 67. Venkat P, Cui C, Chopp M, Zacharek A, Wang F, Landschoot-Ward J, et al. MiR-126 mediates brain endothelial cell exosome treatment-induced neurorestorative effects after stroke in type 2 diabetes mellitus mice. Stroke. 2019;50(10):2865-2874. doi:10.1161/STROKEAHA.119.025371 PMid:31394992 PMCid:PMC6756941
68. Deng Y, Chen D, Gao F, Lv H, Zhang G, Sun X, et al. Exosomes derived from microRNA-138-5p-overexpressing bone marrow-derived mesenchymal stem cells confer neuroprotection to astrocytes following ischemic stroke via inhibition of LCN2. J Biol Eng. 2019;13:1-18. doi:10.1186/s13036-019-0193-0 PMid:31485266 PMCid:PMC6714399
69. Jiang M, Wang H, Jin M, Yang X, Ji H, Jiang Y, et al. Exosomes from MiR-30d-5p-ADSCs reverse acute ischemic stroke-induced, autophagy-mediated brain injury by promoting M2 microglial/macrophage polarization. Cell Physiol Biochem. 2018;47(2):864-878. doi:10.1159/000490078 PMid:29807362
70. Zhao Y, Gan Y, Xu G, Hua K, Liu D. Exosomes from MSCs overexpressing microRNA-223-3p attenuate cerebral ischemia through inhibiting microglial M1 polarization mediated inflammation. Life Sci. 2020;260: 118403. doi:10.1016/j.lfs.2020.118403 PMid:32926923
71. Manuel GE, Johnson T, Liu D. Therapeutic angiogenesis of exosomes for ischemic stroke. Int J Physiol Pathophysiol Pharmacol. 2017;9(6):188-191.
72. Lai RC, Tan SS, Teh BJ, Sze SK, Arslan F, de Kleijn DP, et al. Proteolytic potential of the MSC exosome proteome: Implications for an exosome mediated delivery of therapeutic proteasome. Int J Proteomics. 2012; 2012:971907. doi:10.1155/2012/971907 PMid:22852084 PMCid:PMC3407643
73. Hu GW, Li Q, Niu X, Hu B, Liu J, Zhou SM, et al. Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells attenuate limb ischemia by promoting angiogenesis in mice. Stem Cell Res Ther. 2015;6:1-15. doi:10.1186/scrt546 PMid:26268554 PMCid:PMC4533800
74. Liang X, Zhang L, Wang S, Han Q, Zhao RC. Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a. J Cell Sci. 2016; 129(11): 2182-2189. doi:10.1242/jcs.170373 PMid:27252357
75. Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA, et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell. 2008;15(2):261-271. doi:10.1016/j.devcel.2008.07.002 PMid:18694565 PMCid:PMC2685763
76. Chen F, Du Y, Esposito E, Liu Y, Guo S, Wang X, et al. Effects of focal cerebral ischemia on exosomal versus serum miR126. Transl Stroke Res. 2015; 6:478-484.doi:10.1007/s12975-015-0429-3 PMid:26449616
77. Wang J, Chen S, Zhang W, Chen Y, Bihl JC. Exosomes from miRNA 126‐modified endothelial progenitor cells alleviate brain injury and promote functional recovery after stroke. CNS Neurosci Ther. 2020; 26(12):1255-1265. doi:10.1111/cns.13455 PMid:33009888 PMCid:PMC7702230
78. Xu B, Zhang Y, Du XF, Li J, Zi HX, Bu JW, et al. Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity. Cell Res. 2017; 27(7): 882-897. doi:10.1038/cr.2017.62 PMid:28429770 PMCid:PMC5518987
79. Sharghi-Namini S, Tan E, Ong LLS, Ge R, Asada HH. Dll4-containing exosomes induce capillary sprout retraction in a 3D microenvironment. Sci Rep. 2014; 4(1): 4031.doi:10.1038/srep04031 PMid:24504253 PMCid:PMC3916896
80. Rahman AA, Amruta N, Pinteaux E, Bix GJ. Neurogenesis after stroke: a therapeutic perspective. Transl Stroke Res. 2021;12(1):1-14. doi:10.1007/s12975-020-00841-w PMid:32862401 PMCid:PMC7803692
81. Li Z, Wang J, Zhao C, Ren K, Xia Z, Yu H, et al. Acute blockage of notch signaling by DAPT induces neuroprotection and neurogenesis in the neonatal rat brain after stroke. Transl Stroke Res. 2016;7(2):132-140. doi:10.1007/s12975-015-0441-7 PMid:26691164
82. Zhang W, Cheng J, Vagnerova K, Ivashkova Y, Young J, Cornea A, et al. Effects of androgens on early post-ischemic neurogenesis in mice. Transl Stroke Res. 2014;5:301-311. doi:10.1007/s12975-013-0298-6 PMid:24323721
83. Li WL, Cai HH, Wang B, Chen L, Zhou QG, Luo CX, et al. Chronic fluoxetine treatment improves ischemia induced spatial cognitive deficits through increasing hippocampal neurogenesis after stroke. J Neurosci Res. 2009;87(1):112-122. doi:10.1002/jnr.21829 PMid:18711744
84. Koh SH, Park HH. Neurogenesis in stroke recovery. Transl Stroke Res. 2017;8(1):3-13. doi:10.1007/s12975-016-0460-z PMid:26987852
85. Zhao C, Sun G, Ye P, Li S, Shi Y. MicroRNA let-7d regulates the TLX/microRNA-9 cascade to control neural cell fate and neurogenesis. Sci Rep. 2013; 3(1):1329. doi:10.1038/srep01329 PMid:23435502 PMCid:PMC3580325
86. Meza-Sosa KF, Pedraza-Alva G, Pérez-Martínez L. microRNAs: key triggers of neuronal cell fate. Front Cell Neurosci. 2014;8:175. doi:10.3389/fncel.2014.00175 PMid:25009466 PMCid:PMC4070303
87. Åkerblom M, Sachdeva R, Barde I, Verp S, Gentner B, Trono D, et al. MicroRNA-124 is a subventricular zone neuronal fate determinant. J Neurosci. 2012;32(26):8879-8889. doi:10.1523/JNEUROSCI.0558-12.2012 PMid:22745489 PMCid:PMC4434222
88. Cheng LC, Pastrana E, Tavazoie M, Doetsch F. miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nat Neurosci. 2009; 12(4):399-408. doi:10.1038/nn.2294 PMid:19287386 PMCid:PMC2766245
89. Song Y, Li Z, He T, Qu M, Jiang L, Li W, et al. M2 microglia-derived exosomes protect the mouse brain from ischemia-reperfusion injury via exosomal miR-124. Theranostics. 2019;9(10):2910. doi:10.7150/thno.30879 PMid:31244932 PMCid:PMC6568171
90. Xin H, Li Y, Buller B, Katakowski M, Zhang Y, Wang X, et al. Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells. 2012;30(7):1556-1564. doi:10.1002/stem.1129 PMid:22605481 PMCid:PMC3495063
91. Xin H, Li Y, Liu Z, Wang X, Shang X, Cui Y, et al. MiR-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosome-enriched extracellular particles. Stem Cells. 2013;31(12): 2737-2746. doi:10.1002/stem.1409 PMid:23630198 PMCid:PMC3788061
92. Wei R, Zhang L, Hu W, Shang X, He Y, Zhang W. Zeb2/Axin2-enriched BMSC-derived exosomes promote post-stroke functional recovery by enhancing neurogenesis and neural plasticity. J Mol Neurosci. 2022;72:69-81. doi:10.1007/s12031-021-01887-7 PMid:34401997
93. Zhang G, Zhu Z, Wang H, Yu Y, Chen W, Waqas A, et al. Exosomes derived from human neural stem cells stimulated by interferon gamma improve therapeutic ability in ischemic stroke model. J Adv Res. 2020;24:435-445. doi:10.1016/j.jare.2020.05.017 PMid:32551140 PMCid:PMC7289755
94. Tassew NG, Charish J, Shabanzadeh AP, Luga V, Harada H, Farhani N, et al. Exosomes mediate mobilization of autocrine Wnt10b to promote axonal regeneration in the injured CNS. Cell Rep. 2017; 20(1): 99-111. doi:10.1016/j.celrep.2017.06.009 PMid:28683327
95. Sairanen T, Karjalainen-Lindsberg ML, Paetau A, Ijäs P, Lindsberg PJ. Apoptosis dominant in the periinfarct area of human ischaemic stroke-a possible target of antiapoptotic treatments. Brain. 2006;129(1):189-199. doi:10.1093/brain/awh645 PMid:16272167
96. Radak D, Katsiki N, Resanovic I, Jovanovic A, Sudar-Milovanovic E, Zafirovic S, et al. Apoptosis and acute brain ischemia in ischemic stroke. Curr Vasc Pharmacol. 2017;15(2):115-122. doi:10.2174/1570161115666161104095522 PMid:27823556
97. Xiao Y, Geng F, Wang G, Li X, Zhu J, Zhu W. Bone marrow-derived mesenchymal stem cells-derived exosomes prevent oligodendrocyte apoptosis through exosomal miR-134 by targeting caspase-8. J Cell Biochem. 2019;120(2):2109-2118. doi:10.1002/jcb.27519 PMid:30191592
98. Shen H, Yao X, Li H, Li X, Zhang T, Sun Q, et al. Role of exosomes derived from miR-133b modified MSCs in an experimental rat model of intracerebral hemorrhage. J Mol Neurosci. 2018; 64:421-430. doi:10.1007/s12031-018-1041-2 PMid:29455449
99. Bijian K, Takano T, Papillon J, Le Berre L, Michaud JL, Kennedy CR, et al. Actin cytoskeleton regulates extracellular matrix-dependent survival signals in glomerular epithelial cells. Am J Physiol Renal Physiol. 2005;289(6):F1313-F1323. doi:10.1152/ajprenal.00106.2005 PMid:16014575
100. Xiao B, Chai Y, Lv S, Ye M, Wu M, Xie L, et al. Endothelial cell-derived exosomes protect SH-SY5Y nerve cells against ischemia/reperfusion injury. Int J Mol Med. 2017;40(4):1201-1209. doi:10.3892/ijmm.2017.3106 PMid:28849073 PMCid:PMC5593464
101. Chen KH, Chen CH, Wallace CG, Yuen CM, Kao GS, Chen YL, et al. Intravenous administration of xenogenic adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes markedly reduced brain infarct volume and preserved neurological function in rat after acute ischemic stroke. Oncotarget. 2016;7(46):74537. doi:10.18632/oncotarget.12902 PMid:27793019 PMCid:PMC5342685
102. Zhang Y, Liu J, Su M, Wang X, Xie C. Exosomal microRNA-22-3p alleviates cerebral ischemic injury by modulating KDM6B/BMP2/BMF axis. Stem Cell Res Ther. 2021;12:1-15.doi:10.1186/s13287-020-02091-x PMid:33546766 PMCid:PMC7863295
103. Huang X, Ding J, Li Y, Liu W, Ji J, Wang H, et al. Exosomes derived from PEDF modified adipose-derived mesenchymal stem cells ameliorate cerebral ischemia-reperfusion injury by regulation of autophagy and apoptosis. Exp Cell Res. 2018; 371(1):269-277. doi:10.1016/j.yexcr.2018.08.021 PMid:30142325
104. Zhang Y, Lian L, Fu R, Liu J, Shan X, Jin Y, et al. Microglia: the hub of intercellular communication in ischemic stroke. Front Cell Neurosci. 2022;16:889442. doi:10.3389/fncel.2022.889442 PMid:35518646 PMCid:PMC9062186
105. Li G, Xiao L, Qin H, Zhuang Q, Zhang W, Liu L, et al. RETRACTED ARTICLE: Exosomes-carried microRNA-26b-5p regulates microglia M1 polarization after cerebral ischemia/reperfusion. Cell Cycle. 2020;19(9):1022-1035. doi:10.1080/15384101.2020.1743912 PMid:32208888 PMCid:PMC7217376
106. Liu X, Zhang M, Liu H, Zhu R, He H, Zhou Y, et al. Bone marrow mesenchymal stem cell-derived exosomes attenuate cerebral ischemia-reperfusion injury-induced neuroinflammation and pyroptosis by modulating microglia M1/M2 phenotypes. Exp Neurol. 2021;341:113700. doi:10.1016/j.expneurol.2021.113700 PMid:33741350
107. Zheng Y, He R, Wang P, Shi Y, Zhao L, Liang J. Exosomes from LPS-stimulated macrophages induce neuroprotection and functional improvement after ischemic stroke by modulating microglial polarization. Biomater Sci. 2019;7(5):2037-2049. doi:10.1039/C8BM01449C PMid:30843911
108. Zhao Y, Gan Y, Xu G, Yin G, Liu D. MSCs-derived exosomes attenuate acute brain injury and inhibit microglial inflammation by reversing CysLT2R-ERK1/2 mediated microglia M1 polarization. Neurochem Res. 2020;45(5):1180-1190. doi:10.1007/s11064-020-02998-0 PMid:32112178
109. Zhang Z, Zou X, Zhang R, Xie Y, Feng Z, Li F, et al. Human umbilical cord mesenchymal stem cell-derived exosomal miR-146a-5p reduces microglial-mediated neuroinflammation via suppression of the IRAK1/TRAF6 signaling pathway after ischemic stroke. Aging (Albany NY). 2021;13(2):3060. doi:10.18632/aging.202466 PMid:33479185 PMCid:PMC7880318
110. Yu Y, Zhou H, Xiong Y, Liu J. Exosomal miR-199a-5p derived from endothelial cells attenuates apoptosis and inflammation in neural cells by inhibiting endoplasmic reticulum stress. Brain Res. 2020;1726:146515. doi:10.1016/j.brainres.2019.146515PMid:31634452
111. Li C, Fei K, Tian F, Gao C, Song Y. Adipose-derived mesenchymal stem cells attenuate ischemic brain injuries in rats by modulating miR-21-3p/MAT2B signaling transduction. Croat Med J. 2019;60(5):439-448. doi:10.3325/cmj.2015.56.439
112. Haupt M, Zheng X, Kuang Y, Lieschke S, Janssen L, Bosche B, et al. Lithium modulates miR-1906 levels of mesenchymal stem cell-derived extracellular vesicles contributing to poststroke neuroprotection by toll-like receptor 4 regulation. Stem Cells Transl Med. 2021;10(3):357-373. doi:10.1002/sctm.20-0086 PMid:33146943 PMCid:PMC7900596
113. Mo Y, Sun YY, Liu KY. Autophagy and inflammation in ischemic stroke. Neural Regen Res. 2020;15(8):1388-1396. doi:10.4103/1673-5374.274331 PMid:31997797 PMCid:PMC7059569
114. Chen W, Wang H, Zhu Z, Feng J, Chen L. Exosome-shuttled circSHOC2 from IPASs regulates neuronal autophagy and ameliorates ischemic brain injury via the miR-7670-3p/SIRT1 axis. Mol Ther Nucleic Acids. 2020; 22:657-672. doi:10.1016/j.omtn.2020.09.027 PMid:33230464 PMCid:PMC7581834
115. Kuang Y, Zheng X, Zhang L, Ai X, Venkataramani V, Kilic E, et al. Adipose derived mesenchymal stem cells reduce autophagy in stroke mice by extracellular vesicle transfer of miR 25. J Extracell Vesicles. 2020;10(1):e12024. doi:10.1002/jev2.12024 PMid:33304476 PMCid:PMC7710129
116. Ha D, Yang N, Nadithe V. Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges. Acta Pharm Sin B. 2016;6(4):287-296.doi:10.1016/j.apsb.2016.02.001 PMid:27471669 PMCid:PMC4951582
Send email to the article author

Add your comments about this article
Your username or Email:

CAPTCHA



XML   Persian Abstract   Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Vahidinia Z, Seyed Hosseini E. The Role of Exosomes in Ischemic Stroke: Emerging Diagnostic and Therapeutic Approaches and Challenges in Clinical Translation. Feyz Med Sci J 2026; 30 (1) :112-128
URL: http://feyz.kaums.ac.ir/article-1-5383-en.html


Creative Commons License
This open access journal is licensed under a Creative Commons Attribution-NonCommercial ۴.۰ International License. CC BY-NC ۴. Design and publishing by Kashan University of Medical Sciences.
Copyright ۲۰۲۳© Feyz Medical Sciences Journal. All rights reserved.
Volume 30, Issue 1 (Bimonthly 2026) Back to browse issues page
مجله علوم پزشکی فیض Feyz Medical Sciences Journal
Persian site map - English site map - Created in 0.14 seconds with 46 queries by YEKTAWEB 4741