The role of exosomes in ischemic stroke
DOI:
https://doi.org/10.12775/JEHS.2023.28.01.010Keywords
Exosomes, ischemic stroke, ischemia, microRNA, neurodegenerative processes, neurorestorationAbstract
Introduction and purpose: Ischemic stroke is one of the leading causes of death and disability worldwide. There is an urgent need to develop new treatments and diagnosis. The aim of this review is to gather current knowledge on the potential use of exosomes in the diagnosis and treatment of ischemic stroke. This review was based on available data collected in the Pub Med database and Google Scholar web search engine, using the key words: „Exosomes”, „ischemic stroke”
Description of the state of knowledge: Currently, thanks to the development of knowledge about molecular processes, many studies are conducted on drugs that could limit neurodegenerative processes and support repair processes. Many of the drugs that could be used in treatment show poor penetration through the blood-brain barrier. In studies, exosomes show good penetration through the blood-brain barrier, limit neurodegenerative processes and show neuroregenerative effects. Exosomes are characterized by low immunogenicity and toxicity, and the proteins contained in them are involved in neurogenesis, anti-apoptotic processes and synaptic transmission. In addition, studies have shown exosomes inhibit autophagocytosis and reduce neuronal damage.
Summary: Studies performed on animal models have shown the effectiveness of exosomes in the diagnosis and treatment of ischemic stroke. Further studies are needed to determine the efficacy and safety profile of exosomes in humans.
References
Saini V, Guada L, Yavagal DR. Global Epidemiology of Stroke and Access to Acute Ischemic Stroke Interventions. Neurology. 2021 Nov 16;97(20 Suppl 2):S6-S16. doi: 10.1212/WNL.0000000000012781. PMID: 34785599.
Qiu G, Zheng G, Ge M, Wang J, Huang R, Shu Q, Xu J. Mesenchymal stem cell-derived extracellular vesicles affect disease outcomes via transfer of microRNAs. Stem Cell Res Ther. 2018 Nov 21;9(1):320. doi: 10.1186/s13287-018-1069-9. PMID: 30463593; PMCID: PMC6249826.
Lakhal S, Wood MJ. Exosome nanotechnology: an emerging paradigm shift in drug delivery: exploitation of exosome nanovesicles for systemic in vivo delivery of RNAi heralds new horizons for drug delivery across biological barriers. Bioessays. 2011 Oct;33(10):737-41. doi: 10.1002/bies.201100076. PMID: 21932222.
Zhang Y, Liu Y, Liu H, Tang WH. Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci. 2019 Feb 15;9:19. doi: 10.1186/s13578-019-0282-2. PMID: 30815248; PMCID: PMC6377728.
Pegtel DM, Gould SJ. Exosomes. Annu Rev Biochem. 2019 Jun 20;88:487-514. doi: 10.1146/annurev-biochem- 013118-111902. PMID: 31220978.
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 Jan;72(1):69-81. doi: 10.1007/s12031-021-01887-7. Epub 2021 Aug 16. PMID: 34401997.
Budnik V, Ruiz-Cañada C, Wendler F. Extracellular vesicles round off communication in the nervous system. Nat Rev Neurosci. 2016 Mar;17(3):160-72. doi: 10.1038/nrn.2015.29. PMID: 26891626; PMCID: PMC4989863.
Perez-Gonzalez R, Gauthier SA, Kumar A, Levy E. The exosome secretory pathway transports amyloid precursor protein carboxyl-terminal fragments from the cell into the brain extracellular space. J Biol Chem. 2012 Dec 14;287(51):43108-15. doi: 10.1074/jbc.M112.404467. Epub 2012 Nov 5. PMID: 23129776; PMCID: PMC3522305.
Ji Q, Ji Y, Peng J, Zhou X, Chen X, Zhao H, Xu T, Chen L, Xu Y. Increased Brain-Specific MiR-9 and MiR-124 in the Serum Exosomes of Acute Ischemic Stroke Patients. PLoS One. 2016 Sep 23;11(9):e0163645. doi: 10.1371/journal.pone.0163645. PMID: 27661079; PMCID: PMC5035015.
Zhou J, Chen L, Chen B, Huang S, Zeng C, Wu H, Chen C, Long F. Increased serum exosomal miR-134 expression in the acute ischemic stroke patients. BMC Neurol. 2018 Dec 4;18(1):198. doi: 10.1186/s12883-018-1196-z. PMID: 30514242; PMCID: PMC6278025.
Chen Y, Song Y, Huang J, Qu M, Zhang Y, Geng J, Zhang Z, Liu J, Yang GY. Increased Circulating Exosomal miRNA-223 Is Associated with Acute Ischemic Stroke. Front Neurol. 2017 Feb 27;8:57. doi: 10.3389/fneur.2017.00057. PMID: 28289400; PMCID: PMC5326773.
Luo X, Wang W, Li D, Xu C, Liao B, Li F, Zhou X, Qin W, Liu J. Plasma Exosomal miR-450b-5p as a Possible Biomarker and Therapeutic Target for Transient Ischaemic Attacks in Rats. J Mol Neurosci. 2019 Dec;69(4):516-526. doi: 10.1007/s12031-019-01341-9. Epub 2019 Jul 31. PMID: 31368061.
Li DB, Liu JL, Wang W, Luo XM, Zhou X, Li JP, Cao XL, Long XH, Chen JG, Qin C. Plasma Exosomal miRNA- 122-5p and miR-300-3p as Potential Markers for Transient Ischaemic Attack in Rats. Front Aging Neurosci. 2018 Feb 6;10:24. doi: 10.3389/fnagi.2018.00024. PMID: 29467645; PMCID: PMC5808157.
Zhang GL, Zhu ZH, Wang YZ. Neural stem cell transplantation therapy for brain ischemic stroke: Review and perspectives. World J Stem Cells. 2019 Oct 26;11(10):817-830. doi: 10.4252/wjsc.v11.i10.817. PMID: 31692854; PMCID: PMC6828598.
Chen H, Wang L, Zeng X, Schwarz H, Nanda HS, Peng X, Zhou Y. Exosomes, a New Star for Targeted Delivery. Front Cell Dev Biol. 2021 Oct 8;9:751079. doi: 10.3389/fcell.2021.751079. PMID: 34692704; PMCID: PMC8531489..
Jiang L, Chen W, Ye J, Wang Y. Potential Role of Exosomes in Ischemic Stroke Treatment. Biomolecules. 2022 Jan 11;12(1):115. doi: 10.3390/biom12010115. PMID: 35053263; PMCID: PMC8773818.
Lee JY, Kim E, Choi SM, Kim DW, Kim KP, Lee I, Kim HS. Microvesicles from brain-extract-treated mesenchymal stem cells improve neurological functions in a rat model of ischemic stroke. Sci Rep. 2016 Sep 9;6:33038. doi: 10.1038/srep33038. PMID: 27609711; PMCID: PMC5016792.
Doeppner TR, Herz J, Görgens A, Schlechter J, Ludwig AK, Radtke S, de Miroschedji K, Horn PA, Giebel B, Hermann DM. Extracellular Vesicles Improve Post-Stroke Neuroregeneration and Prevent Postischemic Immunosuppression. Stem Cells Transl Med. 2015 Oct;4(10):1131-43. doi: 10.5966/sctm.2015-0078. Epub 2015 Sep 3. PMID: 26339036; PMCID: PMC4572905.
Chen KH, Chen CH, Wallace CG, Yuen CM, Kao GS, Chen YL, Shao PL, Chen YL, Chai HT, Lin KC, Liu CF, Chang HW, Lee MS, Yip HK. 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 Nov 15;7(46):74537-74556. doi: 10.18632/oncotarget.12902. PMID: 27793019; PMCID: PMC5342685.
Venkat P, Cui C, Chopp M, Zacharek A, Wang F, Landschoot-Ward J, Shen Y, Chen J. MiR-126 Mediates Brain Endothelial Cell Exosome Treatment-Induced Neurorestorative Effects After Stroke in Type 2 Diabetes Mellitus Mice. Stroke. 2019 Oct;50(10):2865-2874. doi: 10.1161/STROKEAHA.119.025371. Epub 2019 Aug 9. PMID: 31394992; PMCID: PMC6756941.
Shintani T, Klionsky DJ. Autophagy in health and disease: a double-edged sword. Science. 2004 Nov 5;306(5698):990-5. doi: 10.1126/science.1099993. PMID: 15528435; PMCID: PMC1705980.
Yu B, Ruan M, Liang T, Huang SW, Liu SJ, Cheng HB, Shen XC. Tetramethylpyrazine phosphate and borneol combination therapy synergistically attenuated ischemia-reperfusion injury of the hypothalamus and striatum via regulation of apoptosis and autophagy in a rat model. Am J Transl Res. 2017 Nov 15;9(11):4807-4820. PMID: 29218081; PMCID: PMC5714767.
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 Sep 15;382(2):111474. doi: 10.1016/j.yexcr.2019.06.019. Epub 2019 Jun 21. PMID: 31229506.
Xin H, Li Y, Buller B, Katakowski M, Zhang Y, Wang X, Shang X, Zhang ZG, Chopp M. Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells. 2012 Jul;30(7):1556-64. doi: 10.1002/stem.1129. PMID: 22605481; PMCID: PMC3495063.
Jiang Y, Xie H, Tu W, Fang H, Ji C, Yan T, Huang H, Yu C, Hu Q, Gao Z, Lv S. Exosomes secreted by HUVECs attenuate hypoxia/reoxygenation-induced apoptosis in neural cells by suppressing miR-21-3p. Am J Transl Res. 2018 Nov 15;10(11):3529-3541. PMID: 30662605; PMCID: PMC6291702.
Tian T, Zhang HX, He CP, Fan S, Zhu YL, Qi C, Huang NP, Xiao ZD, Lu ZH, Tannous BA, Gao J. Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy. Biomaterials. 2018 Jan;150:137-149. doi: 10.1016/j.biomaterials.2017.10.012. Epub 2017 Oct 4. PMID: 29040874.
Lai CP, Mardini O, Ericsson M, Prabhakar S, Maguire C, Chen JW, Tannous BA, Breakefield XO. Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter. ACS Nano. 2014 Jan 28;8(1):483-494. doi: 10.1021/nn404945r. Epub 2014 Jan 9. PMID: 24383518; PMCID: PMC3934350.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Hubert Ciecierski-Koźlarek, Urszula Żurek, Ignacy Tołwiński, Zofia Kędzierska, Weronika Szwed, Klaudia Antkowiak, Klaudia Dadas, Aleksandra Świercz, Dominika Małachowska, Kateryna Shved
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 269
Number of citations: 0