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Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Review Article

Functional Roles of Mesenchymal Stem Cell-derived Exosomes in Ischemic Stroke Treatment

Author(s): Maryam Farzaneh and Seyed Esmaeil Khoshnam*

Volume 19, Issue 1, 2024

Published on: 20 January, 2023

Page: [2 - 14] Pages: 13

DOI: 10.2174/1574888X18666221222123818

Price: $65

Abstract

Stroke is a life-threatening disease and one of the leading causes of death and physical disability worldwide. Currently, no drugs on the market promote neural recovery after stroke insult, and spontaneous remodeling processes are limited to induce recovery in the ischemic regions. Therefore, promoting a cell-based therapy has been needed to elevate the endogenous recovery process. Mesenchymal stem cells (MSCs) have been regarded as candidate cell sources for therapeutic purposes of ischemic stroke, and their therapeutic effects are mediated by exosomes. The microRNA cargo in these extracellular vesicles is mostly responsible for the positive effects. When it comes to the therapeutic viewpoint, MSCsderived exosomes could be a promising therapeutic strategy against ischemic stroke. The aim of this review is to discuss the current knowledge around the potential of MSCs-derived exosomes in the treatment of ischemic stroke.

Graphical Abstract

[1]
Benjamin EJ, Muntner P, Alonso A, et al. Heart disease and stroke Statistics-2019 update a report from the American Heart Association. Circulation 2019; 139(10): e56-e528.
[http://dx.doi.org/10.1161/CIR.0000000000000659] [PMID: 30700139]
[2]
Wardlaw JM, et al. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev 2014; 2014(7): CD000213.
[http://dx.doi.org/10.1002/14651858.CD000213.pub3]
[3]
Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 2016; 387(10029): 1723-31.
[http://dx.doi.org/10.1016/S0140-6736(16)00163-X] [PMID: 26898852]
[4]
Wegener S, Wegener S. Improving cerebral blood flow after arterial recanalization: a novel therapeutic strategy in stroke. Int J Mol Sci 2017; 18(12): 2669.
[http://dx.doi.org/10.3390/ijms18122669] [PMID: 29232823]
[5]
Wang G, Farzaneh M. Mini review; differentiation of human pluripotent stem cells into oocytes. Curr Stem Cell Res Ther 2020; 15(4): 301-7.
[http://dx.doi.org/10.2174/1574888X15666200116100121] [PMID: 31951188]
[6]
Boncoraglio GB, et al. Stem cell transplantation for ischemic stroke Cochrane Database Sys Rev 2019; 2019: CD007231.
[http://dx.doi.org/10.1002/14651858.CD007231.pub3]
[7]
Ebrahimi M, Forouzesh M, Raoufi S, Ramazii M, Ghaedrahmati F, Farzaneh M. Differentiation of human induced pluripotent stem cells into erythroid cells. Stem Cell Res Ther 2020; 11(1): 483.
[http://dx.doi.org/10.1186/s13287-020-01998-9] [PMID: 33198819]
[8]
Witwer KW, Van Balkom BWM, Bruno S, et al. Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for thera-peutic applications. J Extracell Vesicles 2019; 8(1): 1609206.
[http://dx.doi.org/10.1080/20013078.2019.1609206] [PMID: 31069028]
[9]
Xin H, Li Y, Chopp M. Exosomes/miRNAs as mediating cell-based therapy of stroke. Front Cell Neurosci 2014; 8: 377.
[http://dx.doi.org/10.3389/fncel.2014.00377] [PMID: 25426026]
[10]
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): 213-28.
[http://dx.doi.org/10.1038/nrm.2017.125] [PMID: 29339798]
[11]
Badhwar A, Haqqani AS. Biomarker potential of brain‐secreted extracellular vesicles in blood in Alzheimer’s disease. Alzheimers Dement (Amst) 2020; 12(1): e12001.
[http://dx.doi.org/10.1002/dad2.12001] [PMID: 32211497]
[12]
Chaput N, Schartz NEC, André F, et al. Exosomes as potent cell-free peptide-based vaccine. II. Exosomes in CpG adjuvants efficiently prime naive Tc1 lymphocytes leading to tumor rejection. J Immunol 2004; 172(4): 2137-46.
[http://dx.doi.org/10.4049/jimmunol.172.4.2137] [PMID: 14764679]
[13]
Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 2014; 30(1): 255-89.
[http://dx.doi.org/10.1146/annurev-cellbio-101512-122326] [PMID: 25288114]
[14]
Chen J, Chopp M. Exosome therapy for stroke. Stroke 2018; 49(5): 1083-90.
[http://dx.doi.org/10.1161/STROKEAHA.117.018292] [PMID: 29669873]
[15]
a) Maas SLN, Breakefield XO, Weaver AM. Extracellular vesicles: unique intercellular delivery vehicles. Trends Cell Biol 2017; 27(3): 172-88.
[http://dx.doi.org/10.1016/j.tcb.2016.11.003] [PMID: 27979573];
b) Guo M, Yin Z, Chen F, Lei P. Mesenchymal stem cell-derived exosome: a promising alternative in the therapy of Alzheimer’s disease. Alzheimers Res Ther 2020; 12(1): 109.
[http://dx.doi.org/10.1186/s13195-020-00670-x] [PMID: 32928293]
[16]
Hurley JH. ESCRT complexes and the biogenesis of multivesicular bodies. Curr Opin Cell Biol 2008; 20(1): 4-11.
[http://dx.doi.org/10.1016/j.ceb.2007.12.002] [PMID: 18222686]
[17]
Juan T, Fürthauer M. Biogenesis and function of ESCRT-dependent extracellular vesicles. Semin Cell Dev Biol 2018; 74: 66-77.
[http://dx.doi.org/10.1016/j.semcdb.2017.08.022]
[18]
McCullough J, Clippinger AK, Talledge N, et al. Structure and membrane remodeling activity of ESCRT-III helical polymers. Science 2015; 350(6267): 1548-51.
[http://dx.doi.org/10.1126/science.aad8305] [PMID: 26634441]
[19]
Rufino-Ramos D, Albuquerque PR, Carmona V, Perfeito R, Nobre RJ, Pereira de Almeida L. Extracellular vesicles: Novel promising deliv-ery systems for therapy of brain diseases. J Control Release 2017; 262: 247-58.
[http://dx.doi.org/10.1016/j.jconrel.2017.07.001] [PMID: 28687495]
[20]
Mantel PY, Hjelmqvist D, Walch M, et al. Infected erythrocyte-derived extracellular vesicles alter vascular function via regulatory Ago2-miRNA complexes in malaria. Nat Commun 2016; 7(1): 12727.
[http://dx.doi.org/10.1038/ncomms12727] [PMID: 27721445]
[21]
Heydari E, Alishahi M, Ghaedrahmati F, Winlow W, Khoshnam SE, Anbiyaiee A. The role of non-coding RNAs in neuroprotection and angiogenesis following ischemic stroke. Metab Brain Dis 2020; 35(1): 31-43.
[http://dx.doi.org/10.1007/s11011-019-00485-2] [PMID: 31446548]
[22]
Khoshnam SE, Winlow W, Farbood Y, Moghaddam HF, Farzaneh M. Emerging roles of microRNAs in ischemic stroke: as possible thera-peutic agents. J Stroke 2017; 19(2): 166-87.
[http://dx.doi.org/10.5853/jos.2016.01368] [PMID: 28480877]
[23]
Simpson RJ, Kalra H, Mathivanan S. ExoCarta as a resource for exosomal research. J Extracell Vesicles 2012; 1(1): 18374.
[http://dx.doi.org/10.3402/jev.v1i0.18374] [PMID: 24009883]
[24]
Kim DK, Kang B, Kim OY, et al. EVpedia: an integrated database of high-throughput data for systemic analyses of extracellular vesicles. J Extracell Vesicles 2013; 2(1): 20384.
[http://dx.doi.org/10.3402/jev.v2i0.20384] [PMID: 24009897]
[25]
Willms E, Cabañas C, Mäger I, Wood MJA, Vader P. Extracellular vesicle heterogeneity: subpopulations, isolation techniques, and diverse functions in cancer progression. Front Immunol 2018; 9: 738.
[http://dx.doi.org/10.3389/fimmu.2018.00738] [PMID: 29760691]
[26]
Bobrie A, Colombo M, Krumeich S, Raposo G, Théry C. Diverse subpopulations of vesicles secreted by different intracellular mecha-nisms are present in exosome preparations obtained by differential ultracentrifugation. J Extracell Vesicles 2012; 1(1): 18397.
[http://dx.doi.org/10.3402/jev.v1i0.18397] [PMID: 24009879]
[27]
Crescitelli R, Lässer C, Szabó TG, et al. Distinct RNA profiles in subpopulations of extracellular vesicles: apoptotic bodies, microvesicles and exosomes. J Extracell Vesicles 2013; 2(1): 20677.
[http://dx.doi.org/10.3402/jev.v2i0.20677] [PMID: 24223256]
[28]
Borroto-Escuela DO, Agnati LF, Bechter K, Jansson A, Tarakanov AO, Fuxe K. The role of transmitter diffusion and flow versus extracel-lular vesicles in volume transmission in the brain neural–glial networks Philos Trans R Soc Lond B Biol Sci 2015; 370(1672): 20140183.
[http://dx.doi.org/10.1098/rstb.2014.0183] [PMID: 26009762]
[29]
Banigan MG, Kao PF, Kozubek JA, et al. Differential expression of exosomal microRNAs in prefrontal cortices of schizophrenia and bipolar disorder patients. PLoS One 2013; 8(1): e48814.
[http://dx.doi.org/10.1371/journal.pone.0048814] [PMID: 23382797]
[30]
Basso M, Bonetto V. Extracellular vesicles and a novel form of communication in the brain. Front Neurosci 2016; 10: 127.
[http://dx.doi.org/10.3389/fnins.2016.00127] [PMID: 27065789]
[31]
Holm MM, Kaiser J, Schwab ME. Extracellular vesicles: multimodal envoys in neural maintenance and repair. Trends Neurosci 2018; 41(6): 360-72.
[http://dx.doi.org/10.1016/j.tins.2018.03.006] [PMID: 29605090]
[32]
Fauré J, Lachenal G, Court M, et al. Exosomes are released by cultured cortical neurones. Mol Cell Neurosci 2006; 31(4): 642-8.
[http://dx.doi.org/10.1016/j.mcn.2005.12.003] [PMID: 16446100]
[33]
Lachenal G, Pernet-Gallay K, Chivet M, et al. Release of exosomes from differentiated neurons and its regulation by synaptic glutama-tergic activity. Mol Cell Neurosci 2011; 46(2): 409-18.
[http://dx.doi.org/10.1016/j.mcn.2010.11.004] [PMID: 21111824]
[34]
Goldie BJ, Dun MD, Lin M, et al. Activity-associated miRNA are packaged in Map1b-enriched exosomes released from depolarized neu-rons. Nucleic Acids Res 2014; 42(14): 9195-208.
[http://dx.doi.org/10.1093/nar/gku594] [PMID: 25053844]
[35]
Xu B, Zhang Y, Du XF, et al. Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity. Cell Res 2017; 27(7): 882-97.
[http://dx.doi.org/10.1038/cr.2017.62] [PMID: 28429770]
[36]
Wang S, Cesca F, Loers G, et al. Synapsin I is an oligomannose-carrying glycoprotein, acts as an oligomannose-binding lectin, and pro-motes neurite outgrowth and neuronal survival when released via glia-derived exosomes. J Neurosci 2011; 31(20): 7275-90.
[http://dx.doi.org/10.1523/JNEUROSCI.6476-10.2011] [PMID: 21593312]
[37]
Krämer-Albers EM, Bretz N, Tenzer S, et al. Oligodendrocytes secrete exosomes containing major myelin and stress-protective proteins: Trophic support for axons? Proteomics Clin Appl 2007; 1(11): 1446-61.
[http://dx.doi.org/10.1002/prca.200700522] [PMID: 21136642]
[38]
Frühbeis C, Fröhlich D, Kuo WP, Krämer-Albers EM. Extracellular vesicles as mediators of neuron-glia communication. Front Cell Neurosci 2013; 7: 182.
[http://dx.doi.org/10.3389/fncel.2013.00182] [PMID: 24194697]
[39]
Frühbeis C, Fröhlich D, Kuo WP, et al. Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication. PLoS Biol 2013; 11(7): e1001604.
[http://dx.doi.org/10.1371/journal.pbio.1001604] [PMID: 23874151]
[40]
Lafourcade C, Ramírez JP, Luarte J, et al. MIRNAS in astrocyte-derived exosomes as possible mediators of neuronal plasticity: supple-mentary issue: brain plasticity and repair. J Exp Neurosci 2016; 10: S39916.
[http://dx.doi.org/10.4137/JEN.S39916]
[41]
Guitart K, Loers G, Buck F, Bork U, Schachner M, Kleene R. Improvement of neuronal cell survival by astrocyte-derived exosomes under hypoxic and ischemic conditions depends on prion protein. Glia 2016; 64(6): 22963.
[http://dx.doi.org/10.1002/glia.22963] [PMID: 26992135]
[42]
Luarte A, Cisternas P, Caviedes A, et al. Astrocytes at the hub of the stress response: potential modulation of neurogenesis by miRNAs in astrocyte-derived exosomes. Stem Cells Int 2017; 2017: 1719050.
[http://dx.doi.org/10.1155/2017/1719050] [PMID: 29081809]
[43]
Otero-Ortega L, Laso-García F, Gómez-de Frutos MC, et al. White matter repair after extracellular vesicles administration in an experi-mental animal model of subcortical stroke. Sci Rep 2017; 7(1): 44433.
[http://dx.doi.org/10.1038/srep44433] [PMID: 28300134]
[44]
György B, Hung ME, Breakefield XO, Leonard JN. Therapeutic applications of extracellular vesicles: clinical promise and open questions. Annu Rev Pharmacol Toxicol 2015; 55(1): 439-64.
[http://dx.doi.org/10.1146/annurev-pharmtox-010814-124630] [PMID: 25292428]
[45]
Zhuang X, Xiang X, Grizzle W, et al. Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther 2011; 19(10): 1769-79.
[http://dx.doi.org/10.1038/mt.2011.164] [PMID: 21915101]
[46]
Xiong Y, Mahmood A, Chopp M. Emerging potential of exosomes for treatment of traumatic brain injury. Neural Regen Res 2017; 12(1): 19-22.
[http://dx.doi.org/10.4103/1673-5374.198966] [PMID: 28250732]
[47]
András IE, Toborek M. Extracellular vesicles of the blood-brain barrier. Tissue Barriers 2016; 4(1): e1131804.
[http://dx.doi.org/10.1080/21688370.2015.1131804] [PMID: 27141419]
[48]
Grange C, Tapparo M, Bruno S, et al. Biodistribution of mesenchymal stem cell-derived extracellular vesicles in a model of acute kidney injury monitored by optical imaging. Int J Mol Med 2014; 33(5): 1055-63.
[http://dx.doi.org/10.3892/ijmm.2014.1663] [PMID: 24573178]
[49]
Di Rocco G, Baldari S, Toietta G. Towards therapeutic delivery of extracellular vesicles: strategies for in vivo tracking and biodistribution analysis. Stem Cells Int 2016; 2016: 5029619.
[50]
Betzer O, Perets N, Angel A, et al. In vivo neuroimaging of exosomes using gold nanoparticles. ACS Nano 2017; 11(11): 10883-93.
[http://dx.doi.org/10.1021/acsnano.7b04495] [PMID: 28960957]
[51]
Webb RL, Kaiser EE, Scoville SL, et al. Human neural stem cell extracellular vesicles improve tissue and functional recovery in the mu-rine thromboembolic stroke model. Transl Stroke Res 2018; 9(5): 530-9.
[http://dx.doi.org/10.1007/s12975-017-0599-2] [PMID: 29285679]
[52]
Campbell BCV, De Silva DA, Macleod MR, et al. Ischaemic stroke. Nat Rev Dis Primers 2019; 5(1): 70.
[http://dx.doi.org/10.1038/s41572-019-0118-8] [PMID: 31601801]
[53]
Manna I, De Benedittis S, Quattrone A, Maisano D, Iaccino E, Quattrone A. Exosomal miRNAs as potential diagnostic biomarkers in alz-heimer’s disease. Pharmaceuticals (Basel) 2020; 13(9): 243.
[http://dx.doi.org/10.3390/ph13090243] [PMID: 32932746]
[54]
Lin J, Li J, Huang B, et al. Exosomes: novel biomarkers for clinical diagnosis. Sci World J 2015; 2015: 657086.
[http://dx.doi.org/10.1155/2015/657086]
[55]
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): 662-70.
[http://dx.doi.org/10.1177/0963689718816990] [PMID: 30520322]
[56]
Wang W, Li DB, Li RY, 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): 204-12.
[http://dx.doi.org/10.1159/000488365] [PMID: 29627835]
[57]
Zhang G, Chen L, Guo X, et al. Comparative analysis of microRNA expression profiles of exosomes derived from normal and hypoxic preconditioning human neural stem cells by next generation sequencing. J Biomed Nanotechnol 2018; 14(6): 1075-89.
[http://dx.doi.org/10.1166/jbn.2018.2567] [PMID: 29843872]
[58]
Li DB, Liu JL, Wang W, et al. Plasma exosomal miRNA-122-5p and miR-300-3p as potential markers for transient ischaemic attack in rats. Front Aging Neurosci 2018; 10: 24.
[http://dx.doi.org/10.3389/fnagi.2018.00024] [PMID: 29467645]
[59]
Li DB, Liu JL, Wang W, et al. Plasma exosomal miR-422a and miR-125b-2-3p serve as biomarkers for ischemic stroke. Curr Neurovasc Res 2018; 14(4): 330-7.
[http://dx.doi.org/10.2174/1567202614666171005153434] [PMID: 28982331]
[60]
Chen Y, Song Y, Huang J, et al. Increased circulating exosomal miRNA-223 is associated with acute ischemic stroke. Front Neurol 2017; 8: 57.
[http://dx.doi.org/10.3389/fneur.2017.00057] [PMID: 28289400]
[61]
Farzaneh M. Concise Review; Effects of antibiotics and antimycotics on the biological properties of human pluripotent and multipotent stem cells. Curr Stem Cell Res Ther 2021; 16(4): 400-5.
[PMID: 33272189]
[62]
Farzaneh M, Rahimi F, Alishahi M, Khoshnam SE. Paracrine mechanisms involved in mesenchymal stem cell differentiation into cardio-myocytes. Curr Stem Cell Res Ther 2019; 14(1): 9-13.
[http://dx.doi.org/10.2174/1574888X13666180821160421] [PMID: 30152289]
[63]
Alishahi M, Anbiyaiee A, Farzaneh M, Khoshnam SE. Human mesenchymal stem cells for spinal cord injury. Curr Stem Cell Res Ther 2020; 15(4): 340-8.
[http://dx.doi.org/10.2174/1574888X15666200316164051] [PMID: 32178619]
[64]
Harrell C, Fellabaum C, Jovicic N, Djonov V, Arsenijevic N, Volarevic V. Molecular mechanisms responsible for therapeutic potential of mesenchymal stem cell-derived secretome. Cells 2019; 8(5): 467.
[http://dx.doi.org/10.3390/cells8050467] [PMID: 31100966]
[65]
Lu M, Guo J, Wu B, et al. Mesenchymal stem cell-mediated mitochondrial transfer: A therapeutic approach for ischemic stroke. Transl Stroke Res 2021; 12(2): 212-29.
[PMID: 32975692]
[66]
Yong KW, Choi JR, Mohammadi M, Mitha AP, Sanati-Nezhad A, Sen A. Mesenchymal stem cell therapy for ischemic tissues. Stem Cells Int 2018; 2018: 8179075.
[http://dx.doi.org/10.1155/2018/8179075] [PMID: 30402112]
[67]
Dabrowska S, Andrzejewska A, Lukomska B, Janowski M. Neuroinflammation as a target for treatment of stroke using mesenchymal stem cells and extracellular vesicles. J Neuroinflammation 2019; 16(1): 178.
[http://dx.doi.org/10.1186/s12974-019-1571-8] [PMID: 31514749]
[68]
Li X, Huang M, Zhao R, et al. Intravenously delivered allogeneic mesenchymal stem cells bidirectionally regulate inflammation and induce neurotrophic effects in distal middle cerebral artery occlusion rats within the first 7 days after stroke. Cell Physiol Biochem 2018; 46(5): 1951-70.
[http://dx.doi.org/10.1159/000489384] [PMID: 29719282]
[69]
Jaillard A, Hommel M, Moisan A, et al. Autologous mesenchymal stem cells improve motor recovery in subacute ischemic stroke: A randomized clinical trial. Transl Stroke Res 2020; 11(5): 910-23.
[http://dx.doi.org/10.1007/s12975-020-00787-z] [PMID: 32462427]
[70]
Xin H, Li Y, Cui Y, Yang JJ, Zhang ZG, Chopp M. Systemic administration of exosomes released from mesenchymal stromal cells pro-mote functional recovery and neurovascular plasticity after stroke in rats. J Cereb Blood Flow Metab 2013; 33(11): 1711-5.
[http://dx.doi.org/10.1038/jcbfm.2013.152] [PMID: 23963371]
[71]
Buller B, Moore T, Zhang Y, et al. Exosomes from rhesus monkey MSCs promote neuronal growth and myelination. Stroke 2016; 47 (Suppl. 1): A68-8.
[http://dx.doi.org/10.1161/str.47.suppl_1.68]
[72]
Orczykowski ME, Arndt KR, Palitz LE, et al. Cell based therapy enhances activation of ventral premotor cortex to improve recovery fol-lowing primary motor cortex injury. Exp Neurol 2018; 305: 13-25.
[http://dx.doi.org/10.1016/j.expneurol.2018.03.010] [PMID: 29540323]
[73]
Moore TL, et al. Recovery from ischemia in the middle-aged brain: a nonhuman primate model. Neurobiology of aging 2012; 33(3): 619-24.
[http://dx.doi.org/10.1016/j.neurobiolaging.2011.02.005]
[74]
Doeppner TR, Herz J, Görgens A, et al. Extracellular vesicles improve post-stroke neuroregeneration and prevent postischemic immuno-suppression. Stem Cells Transl Med 2015; 4(10): 1131-43.
[http://dx.doi.org/10.5966/sctm.2015-0078] [PMID: 26339036]
[75]
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: 278-87.
[http://dx.doi.org/10.1016/j.omtn.2017.04.010] [PMID: 28624203]
[76]
Xin H, Katakowski M, Wang F, et al. MicroRNA-17–92 cluster in exosomes enhance neuroplasticity and functional recovery after stroke in rats. Stroke 2017; 48(3): 747-53.
[http://dx.doi.org/10.1161/STROKEAHA.116.015204] [PMID: 28232590]
[77]
Nalamolu KR, et al. Exosomes Treatment Mitigates Ischemic Brain Damage but Does Not Improve Post-Stroke Neurological Outcome. Cell Physiol Biochem 2019; 52(6): 1280-91.
[78]
Ling X, Zhang G, Xia Y, 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): 640-54.
[http://dx.doi.org/10.1111/jcmm.14774] [PMID: 31667951]
[79]
Webb RL, Kaiser EE, Jurgielewicz BJ, et al. Human neural stem cell extracellular vesicles improve recovery in a porcine model of ischem-ic stroke. Stroke 2018; 49(5): 1248-56.
[http://dx.doi.org/10.1161/STROKEAHA.117.020353] [PMID: 29650593]
[80]
Xiao B, Chai Y, Lv S, et al. Endothelial cell-derived exosomes protect SH-SY5Y nerve cells against ischemia/reperfusion injury. Int J Mol Med 2017; 40(4): 1201-9.
[http://dx.doi.org/10.3892/ijmm.2017.3106] [PMID: 28849073]
[81]
Zhang ZG, Buller B, Chopp M. Exosomes — beyond stem cells for restorative therapy in stroke and neurological injury. Nat Rev Neurol 2019; 15(4): 193-203.
[http://dx.doi.org/10.1038/s41582-018-0126-4] [PMID: 30700824]
[82]
Catanese L, Tarsia J, Fisher M. Acute ischemic stroke therapy overview. Circ Res 2017; 120(3): 541-58.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.309278] [PMID: 28154103]
[83]
Lapchak PA, Boitano PD, de Couto G, Marbán E. Intravenous xenogeneic human cardiosphere-derived cell extracellular vesicles (exo-somes) improves behavioral function in small-clot embolized rabbits. Exp Neurol 2018; 307: 109-17.
[http://dx.doi.org/10.1016/j.expneurol.2018.06.007] [PMID: 29908146]
[84]
Herberts CA, Kwa MSG, Hermsen HPH. Risk factors in the development of stem cell therapy. J Transl Med 2011; 9(1): 29.
[http://dx.doi.org/10.1186/1479-5876-9-29] [PMID: 21418664]
[85]
Walczak P, Zhang J, Gilad AA, et al. Dual-modality monitoring of targeted intraarterial delivery of mesenchymal stem cells after transient ischemia. Stroke 2008; 39(5): 1569-74.
[http://dx.doi.org/10.1161/STROKEAHA.107.502047] [PMID: 18323495]
[86]
Mateescu B, Kowal EJK, van Balkom BWM, et al. Obstacles and opportunities in the functional analysis of extracellular vesicle RNA – an ISEV position paper. J Extracell Vesicles 2017; 6(1): 1286095.
[http://dx.doi.org/10.1080/20013078.2017.1286095] [PMID: 28326170]
[87]
Collino F, Bruno S, Incarnato D, et al. AKI recovery induced by mesenchymal stromal cell-derived extracellular vesicles carrying mi-croRNAs. J Am Soc Nephrol 2015; 26(10): 2349-60.
[http://dx.doi.org/10.1681/ASN.2014070710] [PMID: 25901032]
[88]
Zhang R, Pan W, Zhang X-P, et al. Cerebral endothelial derived exosomes abolish cognitive impairment induced by ablation of dicer in adult neural progenitor cells. Seman Scholor 2017; 2017: 208581185.
[http://dx.doi.org/10.1161/str.48.suppl_1.wmp48]
[89]
Zhang Y, Chopp M, Liu XS, et al. Exosomes derived from mesenchymal stromal cells promote axonal growth of cortical neurons. Mol Neurobiol 2017; 54(4): 2659-73.
[http://dx.doi.org/10.1007/s12035-016-9851-0] [PMID: 26993303]
[90]
Xin H, Li Y, Buller B, et al. Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contrib-utes to neurite outgrowth. Stem Cells 2012; 30(7): 1556-64.
[http://dx.doi.org/10.1002/stem.1129] [PMID: 22605481]
[91]
Nam JW, Rissland OS, Koppstein D, et al. Global analyses of the effect of different cellular contexts on microRNA targeting. Mol Cell 2014; 53(6): 1031-43.
[http://dx.doi.org/10.1016/j.molcel.2014.02.013] [PMID: 24631284]
[92]
Wang Y, Ma Z, Kan P, Zhang B. The Diagnostic Value of Serum miRNA-221-3p, miRNA-382-5p, and miRNA-4271 in Ischemic Stroke. J Stroke Cerebrovasc Dis 2017; 26(5): 1055-60.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.12.019] [PMID: 28111007]
[93]
Ghoreishy A, Khosravi A, Ghaemmaghami A. Exosomal microRNA and stroke: A review. J Cell Biochem 2019; 120(10): 16352-61.
[http://dx.doi.org/10.1002/jcb.29130] [PMID: 31219202]
[94]
Lei TY, Ye YZ, Zhu XQ, et al. The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke. J Neuroinflammation 2021; 18(1): 25.
[http://dx.doi.org/10.1186/s12974-020-02057-z] [PMID: 33461586]
[95]
Khoshnam SE, Winlow W, Farzaneh M, Farbood Y, Moghaddam HF. Pathogenic mechanisms following ischemic stroke. Neurol Sci 2017; 38(7): 1167-86.
[http://dx.doi.org/10.1007/s10072-017-2938-1] [PMID: 28417216]
[96]
Del Fattore A, Luciano R, Pascucci L, et al. Immunoregulatory effects of mesenchymal stem cell-derived extracellular vesicles on T lym-phocytes. Cell Transplant 2015; 24(12): 2615-27.
[http://dx.doi.org/10.3727/096368915X687543] [PMID: 25695896]
[97]
Blazquez R, Sanchez-Margallo FM, de la Rosa O, et al. Immunomodulatory potential of human adipose mesenchymal stem cells derived exosomes on in vitro stimulated T cells. Front Immunol 2014; 5: 556.
[http://dx.doi.org/10.3389/fimmu.2014.00556] [PMID: 25414703]
[98]
Chen W, Huang Y, Han J, et al. Immunomodulatory effects of mesenchymal stromal cells-derived exosome. Immunol Res 2016; 64(4): 831-40.
[http://dx.doi.org/10.1007/s12026-016-8798-6] [PMID: 27115513]
[99]
Geng W, Tang H, Luo S, et al. Exosomes from miRNA-126-modified ADSCs promotes functional recovery after stroke in rats by improv-ing neurogenesis and suppressing microglia activation. Am J Transl Res 2019; 11(2): 780-92.
[PMID: 30899379]
[100]
Jiang M, Wang H, Jin M, 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): 864-78.
[http://dx.doi.org/10.1159/000490078] [PMID: 29807362]
[101]
Ge X, Guo M, Hu T, et al. Increased microglial exosomal miR-124-3p alleviates neurodegeneration and improves cognitive outcome after rmTBI. Mol Ther 2020; 28(2): 503-22.
[http://dx.doi.org/10.1016/j.ymthe.2019.11.017] [PMID: 31843449]
[102]
Huang S, Ge X, Yu J, et al. Increased miR‐124‐3p in microglial exosomes following traumatic brain injury inhibits neuronal inflamma-tion and contributes to neurite outgrowth via their transfer into neurons. FASEB J 2018; 32(1): 512-28.
[http://dx.doi.org/10.1096/fj.201700673r] [PMID: 28935818]
[103]
Cheng X, Zhang G, Zhang L, et al. Mesenchymal stem cells deliver exogenous miR-21 via exosomes to inhibit nucleus pulposus cell apoptosis and reduce intervertebral disc degeneration. J Cell Mol Med 2018; 22(1): 261-76.
[http://dx.doi.org/10.1111/jcmm.13316] [PMID: 28805297]
[104]
Gorabi AM, Kiaie N, Barreto GE, Read MI, Tafti HA, Sahebkar A. The therapeutic potential of mesenchymal stem cell–derived exosomes in treatment of neurodegenerative diseases. Mol Neurobiol 2019; 56(12): 8157-67.
[http://dx.doi.org/10.1007/s12035-019-01663-0] [PMID: 31197655]
[105]
Canales-Aguirre AA, Reza-Zaldivar EE, Hernández-Sapiéns MA, et al. Mesenchymal stem cell-derived exosomes promote neurogenesis and cognitive function recovery in a mouse model of Alzheimer’s disease. Neural Regen Res 2019; 14(9): 1626-34.
[http://dx.doi.org/10.4103/1673-5374.255978] [PMID: 31089063]
[106]
Katsuda T, Tsuchiya R, Kosaka N, et al. Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exo-somes. Sci Rep 2013; 3(1): 1197-7.
[http://dx.doi.org/10.1038/srep01197] [PMID: 23378928]
[107]
Ding M, Shen Y, Wang P, et al. Exosomes isolated from human umbilical cord mesenchymal stem cells alleviate neuroinflammation and reduce amyloid-beta deposition by modulating microglial activation in Alzheimer’s disease. Neurochem Res 2018; 43(11): 2165-77.
[http://dx.doi.org/10.1007/s11064-018-2641-5] [PMID: 30259257]
[108]
Somoza R, Juri C, Baes M, Wyneken U, Rubio FJ. Intranigral transplantation of epigenetically induced BDNF-secreting human mesenchy-mal stem cells: implications for cell-based therapies in Parkinson’s disease. Biol Blood Marrow Transplant 2010; 16(11): 1530-40.
[http://dx.doi.org/10.1016/j.bbmt.2010.06.006] [PMID: 20542127]
[109]
Jarmalavičiūtė A, Tunaitis V, Pivoraitė U, Venalis A, Pivoriūnas A. Exosomes from dental pulp stem cells rescue human dopaminergic neurons from 6-hydroxy-dopamine–induced apoptosis. Cytotherapy 2015; 17(7): 932-9.
[http://dx.doi.org/10.1016/j.jcyt.2014.07.013] [PMID: 25981557]
[110]
Chen HX, Liang FC, Gu P, et al. Exosomes derived from mesenchymal stem cells repair a Parkinson’s disease model by inducing autoph-agy. Cell Death Dis 2020; 11(4): 288.
[http://dx.doi.org/10.1038/s41419-020-2473-5] [PMID: 32341347]
[111]
Tfilin M, Sudai E, Merenlender A, Gispan I, Yadid G, Turgeman G. Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior. Mol Psychiatry 2010; 15(12): 1164-75.
[http://dx.doi.org/10.1038/mp.2009.110] [PMID: 19859069]
[112]
Kim D, Nishida H, An SY, Shetty AK, Bartosh TJ, Prockop DJ. Chromatographically isolated CD63 + CD81 + extracellular vesicles from mesenchymal stromal cells rescue cognitive impairments after TBI. Proc Natl Acad Sci USA 2016; 113(1): 170-5.
[http://dx.doi.org/10.1073/pnas.1522297113] [PMID: 26699510]
[113]
Zhang Y, Chopp M, Zhang ZG, et al. Systemic administration of cell-free exosomes generated by human bone marrow derived mesen-chymal stem cells cultured under 2D and 3D conditions improves functional recovery in rats after traumatic brain injury. Neurochem Int 2017; 111: 69-81.
[http://dx.doi.org/10.1016/j.neuint.2016.08.003] [PMID: 27539657]
[114]
Williams AM, Dennahy IS, Bhatti UF, et al. Mesenchymal stem cell-derived exosomes provide neuroprotection and improve long-term neurologic outcomes in a swine model of traumatic brain injury and hemorrhagic shock. J Neurotrauma 2019; 36(1): 54-60.
[http://dx.doi.org/10.1089/neu.2018.5711] [PMID: 29690826]
[115]
Zhang Y, Zhang Y, Chopp M, Zhang ZG, Mahmood A, Xiong Y. Mesenchymal stem cell-derived exosomes improve functional recovery in rats after traumatic brain injury: A dose-response and therapeutic window study. Neurorehabil Neural Repair 2020; 34(7): 616-26.
[http://dx.doi.org/10.1177/1545968320926164] [PMID: 32462980]
[116]
Marconi S, Bonaconsa M, Scambi I, et al. Systemic treatment with adipose-derived mesenchymal stem cells ameliorates clinical and pathological features in the amyotrophic lateral sclerosis murine model. Neuroscience 2013; 248: 333-43.
[http://dx.doi.org/10.1016/j.neuroscience.2013.05.034] [PMID: 23727509]
[117]
Riazifar M, Mohammadi MR, Pone EJ, et al. Stem Cell-Derived Exosomes as Nanotherapeutics for Autoimmune and Neurodegenerative Disorders. ACS Nano 2019; 13(6): 6670-88.
[http://dx.doi.org/10.1021/acsnano.9b01004] [PMID: 31117376]
[118]
Drommelschmidt K, Serdar M, Bendix I, et al. Mesenchymal stem cell-derived extracellular vesicles ameliorate inflammation-induced preterm brain injury. Brain Behav Immun 2017; 60: 220-32.
[http://dx.doi.org/10.1016/j.bbi.2016.11.011] [PMID: 27847282]
[119]
Thomi G, Joerger-Messerli M, Haesler V, Muri L, Surbek D, Schoeberlein A. Intranasally administered exosomes from umbilical cord stem cells have preventive neuroprotective effects and contribute to functional recovery after perinatal brain injury. Cells 2019; 8(8): 855.
[http://dx.doi.org/10.3390/cells8080855] [PMID: 31398924]
[120]
Zhang C, Zhang C, Xu Y, Li C, Cao Y, Li P. Exosomes derived from human placenta-derived mesenchymal stem cells improve neurologic function by promoting angiogenesis after spinal cord injury. Neurosci Lett 2020; 739: 135399.
[http://dx.doi.org/10.1016/j.neulet.2020.135399] [PMID: 32979457]
[121]
Xian P, Hei Y, Wang R, et al. Mesenchymal stem cell-derived exosomes as a nanotherapeutic agent for amelioration of inflammation-induced astrocyte alterations in mice. Theranostics 2019; 9(20): 5956-75.
[http://dx.doi.org/10.7150/thno.33872] [PMID: 31534531]
[122]
Tsivion-Visbord H, Perets N, Sofer T, et al. Mesenchymal stem cells derived extracellular vesicles improve behavioral and biochemical deficits in a phencyclidine model of schizophrenia. Transl Psychiatry 2020; 10(1): 305.
[http://dx.doi.org/10.1038/s41398-020-00988-y] [PMID: 32873780]
[123]
Fan B, Li C, Szalad A, et al. Mesenchymal stromal cell-derived exosomes ameliorate peripheral neuropathy in a mouse model of diabetes. Diabetologia 2020; 63(2): 431-43.
[http://dx.doi.org/10.1007/s00125-019-05043-0] [PMID: 31740984]
[124]
Reza-Zaldivar EE, Hernández-Sapiéns MA, Minjarez B, Gutiérrez-Mercado YK, Márquez-Aguirre AL, Canales-Aguirre AA. Potential ef-fects of MSC-derived exosomes in neuroplasticity in Alzheimer’s disease. Front Cell Neurosci 2018; 12: 317.
[http://dx.doi.org/10.3389/fncel.2018.00317] [PMID: 30319358]
[125]
Gandham S, Su X, Wood J, et al. Technologies and standardization in research on extracellular vesicles. Trends Biotechnol 2020; 38(10): 1066-98.
[http://dx.doi.org/10.1016/j.tibtech.2020.05.012] [PMID: 32564882]
[126]
Stremersch S, De Smedt SC, Raemdonck K. Therapeutic and diagnostic applications of extracellular vesicles. J Control Release 2016; 244(Pt B): 167-83.
[http://dx.doi.org/10.1016/j.jconrel.2016.07.054] [PMID: 27491882]
[127]
Yeo RWY, Lai RC, Zhang B, et al. Mesenchymal stem cell: An efficient mass producer of exosomes for drug delivery. Adv Drug Deliv Rev 2013; 65(3): 336-41.
[http://dx.doi.org/10.1016/j.addr.2012.07.001] [PMID: 22780955]
[128]
Gimona M, Pachler K, Laner-Plamberger S, Schallmoser K, Rohde E. Manufacturing of human extracellular vesicle-based therapeutics for clinical use. Int J Mol Sci 2017; 18(6): 1190.
[http://dx.doi.org/10.3390/ijms18061190] [PMID: 28587212]
[129]
Lener T, Gimona M, Aigner L, et al. Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper. J Extracell Vesicles 2015; 4(1): 30087.
[http://dx.doi.org/10.3402/jev.v4.30087] [PMID: 26725829]
[130]
Ophelders DRMG, Wolfs TGAM, Jellema RK, et al. Mesenchymal stromal cell-derived extracellular vesicles protect the fetal brain after hypoxia-ischemia. Stem Cells Transl Med 2016; 5(6): 754-63.
[http://dx.doi.org/10.5966/sctm.2015-0197] [PMID: 27160705]
[131]
Thomi G, Surbek D, Haesler V, Joerger-Messerli M, Schoeberlein A. Exosomes derived from umbilical cord mesenchymal stem cells reduce microglia-mediated neuroinflammation in perinatal brain injury. Stem Cell Res Ther 2019; 10(1): 105.
[http://dx.doi.org/10.1186/s13287-019-1207-z] [PMID: 30898154]
[132]
Sun G, Li G, Li D, et al. hucMSC derived exosomes promote functional recovery in spinal cord injury mice via attenuating inflammation. Mater Sci Eng C 2018; 89: 194-204.
[http://dx.doi.org/10.1016/j.msec.2018.04.006] [PMID: 29752089]
[133]
Ruppert KA, Nguyen TT, Prabhakara KS, et al. Human mesenchymal stromal cell-derived extracellular vesicles modify microglial re-sponse and improve clinical outcomes in experimental spinal cord injury. Sci Rep 2018; 8(1): 480.
[http://dx.doi.org/10.1038/s41598-017-18867-w] [PMID: 29323194]
[134]
Long Q, Upadhya D, Hattiangady B, et al. Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus. Proc Natl Acad Sci USA 2017; 114(17): E3536-45.
[http://dx.doi.org/10.1073/pnas.1703920114] [PMID: 28396435]
[135]
Sisa C, Kholia S, Naylor J, et al. Mesenchymal stromal cell derived extracellular vesicles reduce hypoxia-ischaemia induced perinatal brain injury. Front Physiol 2019; 10: 282.
[http://dx.doi.org/10.3389/fphys.2019.00282] [PMID: 30941062]
[136]
Shiue SJ, Rau RH, Shiue HS, et al. Mesenchymal stem cell exosomes as a cell-free therapy for nerve injury–induced pain in rats. Pain 2019; 160(1): 210-23.
[http://dx.doi.org/10.1097/j.pain.0000000000001395] [PMID: 30188455]

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