Login Register Cart 0
Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

Extracellular Vesicles in the Pathogenesis, Treatment, and Diagnosis of Spinal Cord Injury: A Mini-Review

Author(s): Yang Wang*, Hualiang Xu, Jian Wang, Hanxiao Yi and Yancheng Song

Volume 17, Issue 4, 2022

Published on: 25 May, 2022

Page: [317 - 327] Pages: 11

DOI: 10.2174/1574888X17666220330005937

Price: $65

conference banner
Abstract

Background: Benefiting from in-depth research into stem cells, extracellular vesicles (EVs), which are byproducts of cells and membrane-wrapped microvesicles (30-120 nm) containing lipids, proteins, and nucleic acids, may cast light on the research and development of therapeutics capable of improving the neurological recovery of spinal cord injury (SCI) animals. However, the mechanistic modes of action for EVs in alleviating the lesion size of SCI remain to be solved, thus presenting a tremendous gap existing in translation from the laboratory to the clinic.

Objective: The purpose of this minireview was to cover a wide range of basic views on EVs involved in SCI treatment, including the effects of EVs on the pathogenesis, treatment, and diagnosis of spinal cord injury.

Methods: We searched databases (i.e., PubMed, Web of Science, Scopus, Medline, and EMBASE) and acquired all accessible articles published in the English language within five years. Studies reporting laboratory applications of EVs in the treatment of SCI were included and screened to include studies presenting relevant molecular mechanisms.

Results: This review first summarized the basic role of EVs in cell communication, cell death, inflammatory cascades, scar formation, neuronal regrowth, and angiogenesis after SCI, thereby providing insights into neuroprotection and consolidated theories for future clinical application of EVs.

Conclusion: EVs participate in an extremely wide range of cell activities, play a critical role in cell communication centring neurons, and are considered potential therapies and biomarkers for SCI. miRNAs are the most abundant nucleic acids shipped by EVs and effluent cytokines, and they may represent important messengers of EVs and important factors in SCI treatment.

Keywords: Extracellular vesicles, spinal cord injury, treatment, diagnosis, cell communications, mechanistic modes.

« Previous Next »
Graphical Abstract

[1]
Singh A, Tetreault L, Kalsi-Ryan S, Nouri A, Fehlings MG. Global prevalence and incidence of traumatic spinal cord injury. Clin Epidemiol 2014; 6: 309-31.
[PMID: 25278785]
[2]
Moons WG, Shields GS. Anxiety, not anger, induces inflammatory activity: An avoidance/approach model of immune system activation. Emotion 2015; 15(4): 463-76.
[http://dx.doi.org/10.1037/emo0000055] [PMID: 26053247]
[3]
Rodrigues LF, Moura-Neto V. E Spohr TCLS. Biomarkers in spinal cord injury: From prognosis to treatment. Mol Neurobiol 2018; 55(8): 6436-48.
[http://dx.doi.org/10.1007/s12035-017-0858-y] [PMID: 29307082]
[4]
Hamid R, Averbeck MA, Chiang H, et al. Epidemiology and pathophysiology of neurogenic bladder after spinal cord injury. World J Urol 2018; 36(10): 1517-27.
[http://dx.doi.org/10.1007/s00345-018-2301-z] [PMID: 29752515]
[5]
Charles ED, Fine PR, Stover SL, Wood T, Lott AF, Kronenfeld J. The costs of spinal cord injury. Paraplegia 1978; 15(4): 302-10.
[PMID: 625429]
[6]
Malm T, Loppi S, Kanninen KM. Exosomes in Alzheimer’s disease. Neurochem Int 2016; 97: 193-9.
[http://dx.doi.org/10.1016/j.neuint.2016.04.011] [PMID: 27131734]
[7]
Li Z, Wang Y, Xiao K, Xiang S, Li Z, Weng X. Emerging role of exosomes in the joint diseases. Cell Physiol Biochem 2018; 47(5): 2008-17.
[http://dx.doi.org/10.1159/000491469] [PMID: 29969758]
[8]
Hu Y, Rao SS, Wang ZX, et al. Exosomes from human umbilical cord blood accelerate cutaneous wound healing through miR-21-3p-mediated promotion of angiogenesis and fibroblast function. Theranostics 2018; 8(1): 169-84.
[9]
Zhao B, Zhang Y, Han S, et al. Exosomes derived from human amniotic epithelial cells accelerate wound healing and inhibit scar for-mation. J Mol Histol 2017; 48(2): 121-32.
[http://dx.doi.org/10.1007/s10735-017-9711-x] [PMID: 28229263]
[10]
Tan L, Wu H, Liu Y, Zhao M, Li D, Lu Q. Recent advances of exosomes in immune modulation and autoimmune diseases. Autoimmunity 2016; 49(6): 357-65.
[11]
Goncalves MB, Malmqvist T, Clarke E, et al. Neuronal RARβ signaling modulates PTEN activity directly in neurons and via exosome transfer in astrocytes to prevent glial scar formation and induce spinal cord regeneration. J Neurosci 2015; 35(47): 15731-45.
[http://dx.doi.org/10.1523/JNEUROSCI.1339-15.2015] [PMID: 26609164]
[12]
Zhou X, Chu X, Yuan H, et al. Mesenchymal stem cell derived EVs mediate neuroprotection after spinal cord injury in rats via the mi-croRNA-21-5p/FasL gene axis. Biomed Pharmacother 2019; 115: 108818.
[http://dx.doi.org/10.1016/j.biopha.2019.108818] [PMID: 31102912]
[13]
Sharma P, Mesci P, Carromeu C, et al. Exosomes regulate neurogenesis and circuit assembly. Proc Natl Acad Sci USA 2019; 116(32): 16086-94.
[http://dx.doi.org/10.1073/pnas.1902513116] [PMID: 31320591]
[14]
Dutta D, Khan N, Wu J, Jay SM. Extracellular vesicles as an emerging frontier in spinal cord injury pathobiology and therapy. Trends Neurosci 2021; 44(6): 492-506.
[http://dx.doi.org/10.1016/j.tins.2021.01.003] [PMID: 33581883]
[15]
Guo S, Redenski I, Levenberg S. Spinal cord repair: From cells and tissue engineering to extracellular vesicles. Cells 2021; 10(8): 1872.
[http://dx.doi.org/10.3390/cells10081872] [PMID: 34440641]
[16]
Wang X, Botchway BOA, Zhang Y, Yuan J, Liu X. Combinational treatment of bioscaffolds and extracellular vesicles in spinal cord inju-ry. Front Mol Neurosci 2019; 12: 81.
[http://dx.doi.org/10.3389/fnmol.2019.00081] [PMID: 31031590]
[17]
Spejo AB, Chiarotto GB, Ferreira ADF, et al. Neuroprotection and immunomodulation following intraspinal axotomy of motoneurons by treatment with adult mesenchymal stem cells. J Neuroinflammation 2018; 15(1): 230.
[http://dx.doi.org/10.1186/s12974-018-1268-4] [PMID: 30107848]
[18]
Dos Santos Ramalho B, Pestana MF, Prins AC, et al. Effects of different doses of mesenchymal stem cells on functional recovery after compressive spinal-cord injury in mice. Neuroscience 2019; 400: 17-32.
[http://dx.doi.org/10.1016/j.neuroscience.2018.12.005] [PMID: 30553796]
[19]
Takahashi S, Nakagawa K, Tomiyasu M, et al. Mesenchymal stem cell-based therapy improves lower limb movement after spinal cord ischemia in rats. Ann Thorac Surg 2018; 105(5): 1523-30.
[http://dx.doi.org/10.1016/j.athoracsur.2017.12.014] [PMID: 29337123]
[20]
Maldonado-Lasunción I, Verhaagen J, Oudega M. Mesenchymal stem cell-macrophage choreography supporting spinal cord repair. Neurotherapeutics 2018; 15(3): 578-87.
[http://dx.doi.org/10.1007/s13311-018-0629-0] [PMID: 29728851]
[21]
Trams EG, Lauter CJ, Salem N Jr, Heine U. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta 1981; 645(1): 63-70.
[http://dx.doi.org/10.1016/0005-2736(81)90512-5] [PMID: 6266476]
[22]
Arenaccio C, Federico M. The multifaceted functions of exosomes in health and disease: An overview. Adv Exp Med Biol 2017; 998: 3-19.
[http://dx.doi.org/10.1007/978-981-10-4397-0_1] [PMID: 28936729]
[23]
Pan BT, Teng K, Wu C, Adam M, Johnstone RM. Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J Cell Biol 1985; 101(3): 942-8.
[http://dx.doi.org/10.1083/jcb.101.3.942] [PMID: 2993317]
[24]
Harding C, Heuser J, Stahl P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol 1983; 97(2): 329-39.
[http://dx.doi.org/10.1083/jcb.97.2.329] [PMID: 6309857]
[25]
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]
[26]
Meldolesi J. Exosomes and ectosomes in intercellular communication. Curr Biol 2018; 28(8): R435-44.
[http://dx.doi.org/10.1016/j.cub.2018.01.059] [PMID: 29689228]
[27]
Théry C, Zitvogel L, Amigorena S. Exosomes: Composition, biogenesis and function. Nat Rev Immunol 2002; 2(8): 569-79.
[http://dx.doi.org/10.1038/nri855] [PMID: 12154376]
[28]
Ageta H, Ageta-Ishihara N, Hitachi K, et al. UBL3 modification influences protein sorting to small extracellular vesicles. Nat Commun 2018; 9(1): 3936.
[http://dx.doi.org/10.1038/s41467-018-06197-y] [PMID: 30258067]
[29]
van Niel G, Raposo G, Candalh C, et al. Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology 2001; 121(2): 337-49.
[http://dx.doi.org/10.1053/gast.2001.26263] [PMID: 11487543]
[30]
Theos AC, Truschel ST, Tenza D, et al. A lumenal domain-dependent pathway for sorting to intralumenal vesicles of multivesicular endo-somes involved in organelle morphogenesis. Dev Cell 2006; 10(3): 343-54.
[http://dx.doi.org/10.1016/j.devcel.2006.01.012] [PMID: 16516837]
[31]
Baietti MF, Zhang Z, Mortier E, et al. Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat Cell Biol 2012; 14(7): 677-85.
[http://dx.doi.org/10.1038/ncb2502] [PMID: 22660413]
[32]
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] [PMID: 28807885]
[33]
Fortunato O, Gasparini P, Boeri M, Sozzi G. Exo-miRNAs as a new tool for liquid biopsy in lung cancer. Cancers (Basel) 2019; 11(6): 888.
[http://dx.doi.org/10.3390/cancers11060888] [PMID: 31242686]
[34]
Huang D, Chen J, Hu D, et al. Advances in biological function and clinical application of small extracellular vesicle membrane proteins. Front Oncol 2021; 11: 675940.
[http://dx.doi.org/10.3389/fonc.2021.675940] [PMID: 34094979]
[35]
Kourembanas S. Exosomes: Vehicles of intercellular signaling, biomarkers, and vectors of cell therapy. Annu Rev Physiol 2015; 77: 13-27.
[http://dx.doi.org/10.1146/annurev-physiol-021014-071641] [PMID: 25293529]
[36]
Raposo G, Stoorvogel W. Extracellular vesicles: Exosomes, microvesicles, and friends. J Cell Biol 2013; 200(4): 373-83.
[http://dx.doi.org/10.1083/jcb.201211138] [PMID: 23420871]
[37]
Kosaka N, Iguchi H, Hagiwara K, Yoshioka Y, Takeshita F, Ochiya T. Neutral sphingomyelinase 2 (nSMase2)-dependent exosomal trans-fer of angiogenic microRNAs regulate cancer cell metastasis. J Biol Chem 2013; 288(15): 10849-59.
[http://dx.doi.org/10.1074/jbc.M112.446831] [PMID: 23439645]
[38]
Villarroya-Beltri C, Gutiérrez-Vázquez C, Sánchez-Cabo F, et al. Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat Commun 2013; 4: 2980.
[http://dx.doi.org/10.1038/ncomms3980] [PMID: 24356509]
[39]
Zhang J, Li S, Li L, et al. Exosome and exosomal microRNA: Trafficking, sorting, and function. Genom Proteom Bioinf 2015; 13(1): 17-24.
[http://dx.doi.org/10.1016/j.gpb.2015.02.001] [PMID: 25724326]
[40]
Squadrito ML, Baer C, Burdet F, et al. Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells. Cell Rep 2014; 8(5): 1432-46.
[http://dx.doi.org/10.1016/j.celrep.2014.07.035] [PMID: 25159140]
[41]
Koppers-Lalic D, Hackenberg M, Bijnsdorp IV, et al. Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes. Cell Rep 2014; 8(6): 1649-58.
[http://dx.doi.org/10.1016/j.celrep.2014.08.027] [PMID: 25242326]
[42]
Raffo-Romero A, Arab T, Al-Amri IS, et al. Medicinal Leech CNS as a model for exosome studies in the crosstalk between microglia and neurons. Int J Mol Sci 2018; 19(12): 4124.
[http://dx.doi.org/10.3390/ijms19124124] [PMID: 30572617]
[43]
Chen X, Qian B, Kong X, et al. A20 protects neuronal apoptosis stimulated by lipopolysaccharide-induced microglial exosomes. Neurosci Lett 2019; 712: 134480.
[http://dx.doi.org/10.1016/j.neulet.2019.134480] [PMID: 31493550]
[44]
Song Y, Li Z, He T, et al. M2 microglia-derived exosomes protect the mouse brain from ischemia-reperfusion injury via exosomal miR-124. Theranostics 2019; 9(10): 2910-23.
[http://dx.doi.org/10.7150/thno.30879] [PMID: 31244932]
[45]
Huang S, Ge X, Yu J, et al. Increased miR-124-3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation 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]
[46]
Asai H, Ikezu S, Tsunoda S, et al. Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat Neurosci 2015; 18(11): 1584-93.
[http://dx.doi.org/10.1038/nn.4132] [PMID: 26436904]
[47]
Cheng YY, Zhao HK, Chen LW, et al. Reactive astrocytes increase expression of proNGF in the mouse model of contused spinal cord injury. Neurosci Res 2020; 157: 34-43.
[http://dx.doi.org/10.1016/j.neures.2019.07.007] [PMID: 31348996]
[48]
Taylor AR, Robinson MB, Gifondorwa DJ, Tytell M, Milligan CE. Regulation of heat shock protein 70 release in astrocytes: Role of sig-naling kinases. Dev Neurobiol 2007; 67(13): 1815-29.
[http://dx.doi.org/10.1002/dneu.20559] [PMID: 17701989]
[49]
Garré JM, Retamal MA, Cassina P, et al. FGF-1 induces ATP release from spinal astrocytes in culture and opens pannexin and connexin hemichannels. Proc Natl Acad Sci USA 2010; 107(52): 22659-64.
[http://dx.doi.org/10.1073/pnas.1013793107] [PMID: 21148774]
[50]
Adolf A, Rohrbeck A, Münster-Wandowski A, et al. Release of astroglial vimentin by extracellular vesicles: Modulation of binding and internalization of C3 transferase in astrocytes and neurons. Glia 2019; 67(4): 703-17.
[51]
Gosselin RD, Meylan P, Decosterd I. Extracellular microvesicles from astrocytes contain functional glutamate transporters: Regulation by protein kinase C and cell activation. Front Cell Neurosci 2013; 7: 251.
[http://dx.doi.org/10.3389/fncel.2013.00251] [PMID: 24368897]
[52]
Hervera A, De Virgiliis F, Palmisano I, et al. Reactive oxygen species regulate axonal regeneration through the release of exosomal NADPH oxidase 2 complexes into injured axons. Nat Cell Biol 2018; 20(3): 307-19.
[http://dx.doi.org/10.1038/s41556-018-0039-x] [PMID: 29434374]
[53]
Goncalves MB, Wu Y, Trigo D, et al. Retinoic acid synthesis by NG2 expressing cells promotes a permissive environment for axonal outgrowth. Neurobiol Dis 2018; 111: 70-9.
[http://dx.doi.org/10.1016/j.nbd.2017.12.016] [PMID: 29274429]
[54]
Frühbeis C, Kuo-Elsner WP, Müller C, et al. Oligodendrocytes support axonal transport and maintenance via exosome secretion. PLoS Biol 2020; 18(12): e3000621.
[http://dx.doi.org/10.1371/journal.pbio.3000621] [PMID: 33351792]
[55]
O Shea TM, Burda JE, Sofroniew MV. Cell biology of spinal cord injury and repair. J Clin Invest 2017; 127(9): 3259-70.
[http://dx.doi.org/10.1172/JCI90608] [PMID: 28737515]
[56]
Jiang HH, Xiao MY, Xu Y, et al. Systemic administration of exosomes released from mesenchymal stromal cells attenuates apoptosis, inflammation and promotes angiogenesis after contusion spinal cord injury in rats. J Neurotrauma 2017; 24(34): 3388-96.
[57]
Gu J, Jin ZS, Wang CM, Yan XF, Mao YQ, Chen S. Bone marrow mesenchymal stem cell-derived exosomes improve spinal cord function after injury in rats by activating autophagy 2020; 14: 1621-31.
[58]
Rong Y, Liu W, Wang J, et al. Neural stem cell-derived small extracellular vesicles attenuate apoptosis and neuroinflammation after trau-matic spinal cord injury by activating autophagy. Cell Death Dis 2019; 10(5): 340.
[http://dx.doi.org/10.1038/s41419-019-1571-8] [PMID: 31000697]
[59]
Tsai MJ, Liou DY, Lin YR, et al. Attenuating spinal cord injury by conditioned medium from bone marrow mesenchymal stem cells. J Clin Med 2018; 8(1): 23.
[http://dx.doi.org/10.3390/jcm8010023] [PMID: 30585207]
[60]
Clevers H, Nusse R. Wnt/β-catenin signaling and disease. Cell 2012; 149(6): 1192-205.
[http://dx.doi.org/10.1016/j.cell.2012.05.012] [PMID: 22682243]
[61]
van Amerongen R, Mikels A, Nusse R. Alternative wnt signaling is initiated by distinct receptors. Sci Signal 2008; 1(35): re9.
[http://dx.doi.org/10.1126/scisignal.135re9] [PMID: 18765832]
[62]
Li C, Jiao G, Wu W, et al. Exosomes from bone marrow mesenchymal stem cells inhibit neuronal apoptosis and promote motor function recovery via the Wnt/β-catenin signaling pathway. Cell Transplant 2019; 28(11): 1373-83.
[http://dx.doi.org/10.1177/0963689719870999] [PMID: 31423807]
[63]
Luther KM, Haar L, McGuinness M, et al. Exosomal miR-21a-5p mediates cardioprotection by mesenchymal stem cells. J Mol Cell Cardiol 2018; 119: 125-37.
[http://dx.doi.org/10.1016/j.yjmcc.2018.04.012] [PMID: 29698635]
[64]
Yin XH, Han YL, Zhuang Y, Yan JZ, Li C. Geldanamycin inhibits Fas signaling pathway and protects neurons against ischemia. Neurosci Res 2017; 124: 33-9.
[http://dx.doi.org/10.1016/j.neures.2017.05.003] [PMID: 28522336]
[65]
Schleicher RI, Reichenbach F, Kraft P, et al. Platelets induce apoptosis via membrane-bound FasL. Blood 2015; 126(12): 1483-93.
[http://dx.doi.org/10.1182/blood-2013-12-544445] [PMID: 26232171]
[66]
Kang J, Zhang C, Zhi Z, et al. Stem-like cells of various origins showed therapeutic effect to improve the recovery of spinal cord injury. Artif Cells Nanomed Biotechnol 2020; 48(1): 627-38.
[http://dx.doi.org/10.1080/21691401.2020.1725031] [PMID: 32054316]
[67]
Kang J, Li Z, Zhi Z, Wang S, Xu G. MiR-21 derived from the exosomes of MSCs regulates the death and differentiation of neurons in patients with spinal cord injury. Gene Ther 2019; 26(12): 491-503.
[http://dx.doi.org/10.1038/s41434-019-0101-8] [PMID: 31570818]
[68]
Flores AI, Narayanan SP, Morse EN, et al. Constitutively active Akt induces enhanced myelination in the CNS. J Neurosci 2008; 28(28): 7174-83.
[http://dx.doi.org/10.1523/JNEUROSCI.0150-08.2008] [PMID: 18614687]
[69]
Xu G, Ao R, Zhi Z, Jia J, Yu B. miR-21 and miR-19b delivered by hMSC-derived EVs regulate the apoptosis and differentiation of neu-rons in patients with spinal cord injury. J Cell Physiol 2019; 234(7): 10205-17.
[http://dx.doi.org/10.1002/jcp.27690] [PMID: 30387159]
[70]
Wang Z, Song Y, Han X, Qu P, Wang W. Long noncoding RNA PTENP1 affects the recovery of spinal cord injury by regulating the ex-pression of miR-19b and miR-21. J Cell Physiol 2020; 235(4): 3634-45.
[http://dx.doi.org/10.1002/jcp.29253] [PMID: 31583718]
[71]
Wang J, Rong Y, Ji C, et al. MicroRNA-421-3p-abundant small extracellular vesicles derived from M2 bone marrow-derived macrophages attenuate apoptosis and promote motor function recovery via inhibition of mTOR in spinal cord injury. J Nanobiotech 2020; 18(1): 72.
[http://dx.doi.org/10.1186/s12951-020-00630-5] [PMID: 32404105]
[72]
Li D, Zhang P, Yao X, et al. Exosomes derived from miR-133b-modified mesenchymal stem cells promote recovery after spinal cord injury. Front Neurosci 2018; 12: 845.
[http://dx.doi.org/10.3389/fnins.2018.00845] [PMID: 30524227]
[73]
Huang JH, Xu Y, Yin XM, Lin FY. Exosomes derived from miR-126-modified MSCs promote angiogenesis and neurogenesis and attenu-ate apoptosis after spinal cord injury in rats. Neuroscience 2020; 424: 133-45.
[http://dx.doi.org/10.1016/j.neuroscience.2019.10.043] [PMID: 31704348]
[74]
Luo Y, Xu T, Liu W, et al. Exosomes derived from GIT1-overexpressing bone marrow mesenchymal stem cells promote traumatic spinal cord injury recovery in a rat model. Int J Neurosci 2021; 131(2): 170-82.
[PMID: 32223487]
[75]
Huang W, Qu M, Li L, Liu T, Lin M, Yu X. SiRNA in MSC-derived exosomes silences CTGF gene for locomotor recovery in spinal cord injury rats. Stem Cell Res Ther 2021; 12(1): 334.
[http://dx.doi.org/10.1186/s13287-021-02401-x] [PMID: 34112262]
[76]
Gao ZS, Zhang CJ, Xia N, et al. Berberine-loaded M2 macrophage-derived exosomes for spinal cord injury therapy. Acta Biomater 2021; 126: 211-23.
[http://dx.doi.org/10.1016/j.actbio.2021.03.018] [PMID: 33722788]
[77]
Huang J-H, Fu C-H, Xu Y, Yin X-M, Cao Y, Lin FY. Extracellular vesicles derived from epidural fat-mesenchymal stem cells attenuate NLRP3 inflammasome activation and improve functional recovery after spinal cord injury. Neurochem Res 2020; 45(4): 760-71.
[http://dx.doi.org/10.1007/s11064-019-02950-x] [PMID: 31953741]
[78]
Ijaz S, Mohammed I, Gholaminejhad M, Mokhtari T, Akbari M, Hassanzadeh G. Modulating pro-inflammatory cytokines, tissue damage magnitude, and motor deficit in spinal cord injury with subventricular zone-derived extracellular vesicles. J Mol Neurosci 2020; 70(3): 458-66.
[http://dx.doi.org/10.1007/s12031-019-01437-2] [PMID: 31768946]
[79]
Mohammed I, Ijaz S, Mokhtari T, et al. Subventricular zone-derived extracellular vesicles promote functional recovery in rat model of spinal cord injury by inhibition of NLRP3 inflammasome complex formation. Metab Brain Dis 2020; 35(5): 809-18.
[http://dx.doi.org/10.1007/s11011-020-00563-w] [PMID: 32185593]
[80]
Li C, Li X, Zhao B, Wang C. Exosomes derived from miR-544-modified mesenchymal stem cells promote recovery after spinal cord inju-ry. Arch Physiol Biochem 2020; 126(4): 369-75.
[http://dx.doi.org/10.1080/13813455.2019.1691601] [PMID: 32141339]
[81]
Pachler K, Ketterl N, Desgeorges A, et al. An in vitro potency assay for monitoring the immunomodulatory potential of stromal cell-derived extracellular vesicles. Int J Mol Sci 2017; 18(7): 1413.
[http://dx.doi.org/10.3390/ijms18071413] [PMID: 28671586]
[82]
Rong Y, Liu W, Lv C, et al. Neural stem cell small extracellular vesicle-based delivery of 14-3-3t reduces apoptosis and neuroinflamma-tion following traumatic spinal cord injury by enhancing autophagy by targeting Beclin-1. Aging (Albany NY) 2019; 11(18): 7723-45.
[http://dx.doi.org/10.18632/aging.102283] [PMID: 31563124]
[83]
Kim M, Jo H, Kwon Y, et al. MiR-154-5p-MCP1 axis regulates allergic inflammation by mediating cellular interactions. Front Immunol 2021; 12: 663726.
[http://dx.doi.org/10.3389/fimmu.2021.663726] [PMID: 34135893]
[84]
Zhao C, Zhou X, Qiu J, et al. Exosomes derived from bone marrow mesenchymal stem cells inhibit complement activation in rats with spinal cord injury. Drug Des Devel Ther 2019; 13: 3693-704.
[http://dx.doi.org/10.2147/DDDT.S209636] [PMID: 31695336]
[85]
Lankford KL, Arroyo EJ, Nazimek K, Bryniarski K, Askenase PW, Kocsis JD. Intravenously delivered mesenchymal stem cell-derived exosomes target M2-type macrophages in the injured spinal cord. PLoS One 2018; 13(1): e190358.
[86]
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]
[87]
Chang Q, Hao Y, Wang Y, Zhou Y, Zhuo H, Zhao G. Bone marrow mesenchymal stem cell-derived exosomal microRNA-125a promotes M2 macrophage polarization in spinal cord injury by downregulating IRF5. Brain Res Bull 2021; 170: 199-210.
[http://dx.doi.org/10.1016/j.brainresbull.2021.02.015] [PMID: 33609602]
[88]
Li R, Zhao K, Ruan Q, Meng C, Yin F. Bone marrow mesenchymal stem cell-derived exosomal microRNA-124-3p attenuates neurological damage in spinal cord ischemia-reperfusion injury by downregulating Ern1 and promoting M2 macrophage polarization. Arthritis Res Ther 2020; 22(1): 75.
[http://dx.doi.org/10.1186/s13075-020-2146-x] [PMID: 32272965]
[89]
Ge X, Tang P, Rong Y, et al. Exosomal miR-155 from M1-polarized macrophages promotes EndoMT and impairs mitochondrial function via activating NF-κB signaling pathway in vascular endothelial cells after traumatic spinal cord injury. Redox Biol 2021; 41: 101932.
[http://dx.doi.org/10.1016/j.redox.2021.101932] [PMID: 33714739]
[90]
Zhao L, Jiang X, Shi J, et al. Exosomes derived from bone marrow mesenchymal stem cells overexpressing microRNA-25 protect spinal cords against transient ischemia. J Thorac Cardiovasc Surg 2019; 157(2): 508-17.
[http://dx.doi.org/10.1016/j.jtcvs.2018.07.095] [PMID: 30224076]
[91]
Ma K, Xu H, Zhang J, et al. Insulin-like growth factor-1 enhances neuroprotective effects of neural stem cell exosomes after spinal cord injury via an miR-219a-2-3p/YY1 mechanism. Aging (Albany NY) 2019; 11(24): 12278-94.
[http://dx.doi.org/10.18632/aging.102568] [PMID: 31848325]
[92]
Hazelton I, Yates A, Dale A, et al. Exacerbation of acute traumatic brain injury by circulating extracellular vesicles. J Neurotrauma 2018; 35(4): 639-51.
[http://dx.doi.org/10.1089/neu.2017.5049] [PMID: 29149810]
[93]
Anderson MA, Burda JE, Ren Y, et al. Astrocyte scar formation aids central nervous system axon regeneration. Nature 2016; 532(7598): 195-200.
[http://dx.doi.org/10.1038/nature17623] [PMID: 27027288]
[94]
Sofroniew MV, Vinters HV, Vinters HV, Vinters HV. Astrocytes: Biology and pathology. Acta Neuropathol 2010; 119(1): 7-35.
[http://dx.doi.org/10.1007/s00401-009-0619-8] [PMID: 20012068]
[95]
Liu W, Wang Y, Gong F, et al. Exosomes derived from bone mesenchymal stem cells repair traumatic spinal cord injury by suppressing the activation of A1 neurotoxic reactive astrocytes. J Neurotrauma 2019; 36(3): 469-84.
[http://dx.doi.org/10.1089/neu.2018.5835] [PMID: 29848167]
[96]
Guo S, Perets N, Betzer O, et al. Intranasal delivery of mesenchymal stem cell derived exosomes loaded with phosphatase and tensin homolog siRNA repairs complete spinal cord injury. ACS Nano 2019; 13(9): 10015-28.
[http://dx.doi.org/10.1021/acsnano.9b01892] [PMID: 31454225]
[97]
Wang L, Pei S, Han L, et al. Mesenchymal stem cell-derived exosomes reduce A1 astrocytes via downregulation of Phosphorylated NFκB P65 subunit in spinal cord injury. Cell Physiol Biochem 2018; 50(4): 1535-59.
[http://dx.doi.org/10.1159/000494652] [PMID: 30376671]
[98]
Romanelli P, Bieler L, Scharler C, et al. Extracellular vesicles can deliver anti-inflammatory and anti-scarring activities of mesenchymal stromal cells after spinal cord injury. Front Neurol 2019; 10: 1225.
[http://dx.doi.org/10.3389/fneur.2019.01225] [PMID: 31849808]
[99]
Men Y, Yelick J, Jin S, et al. Exosome reporter mice revealed the involvement of exosomes in mediating neurons to astroglia communica-tion in the CNS. Nat Commun 2019; 10(1): 4118-36.
[http://dx.doi.org/10.1038/s41467-019-11534-w] [PMID: 31511506]
[100]
Zhou X, He X, Ren Y. Function of microglia and macrophages in secondary damage after spinal cord injury. Neural Regen Res 2014; 9(20): 1787-95.
[http://dx.doi.org/10.4103/1673-5374.143423] [PMID: 25422640]
[101]
Pan J, Jin JL, Ge HM, et al. Malibatol A regulates microglia M1/M2 polarization in experimental stroke in a PPARγ-dependent manner. J Neuroinflammation 2015; 12(1): 51.
[http://dx.doi.org/10.1186/s12974-015-0270-3] [PMID: 25889216]
[102]
Liu W, Rong Y, Wang J, et al. Exosome-shuttled miR-216a-5p from hypoxic preconditioned mesenchymal stem cells repair traumatic spinal cord injury by shifting microglial M1/M2 polarization. J Neuroinflammation 2020; 17(1): 47.
[http://dx.doi.org/10.1186/s12974-020-1726-7] [PMID: 32019561]
[103]
Zhang M, Wang L, Huang S, He X. Exosomes with high level of miR-181c from bone marrow-derived mesenchymal stem cells inhibit inflammation and apoptosis to alleviate spinal cord injury. J Mol Histol 2021; 52(2): 301-11.
[http://dx.doi.org/10.1007/s10735-020-09950-0] [PMID: 33548000]
[104]
Shao M, Jin M, Xu S, et al. Exosomes from long noncoding RNA-Gm37494-ADSCs repair spinal cord injury via shifting microglial M1/M2 polarization. Inflammation 2020; 43(4): 1536-47.
[http://dx.doi.org/10.1007/s10753-020-01230-z] [PMID: 32307615]
[105]
Emily B. Harrison, Colleen G Hochfelder, Benjamin G Lamberty, et al. Traumatic brain injury increases the levels of miR-21 in extracellu-lar vesicles: Implications for neuroinflammation. FEBS Open Bio 2016; 8(6): 835-46.
[106]
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-UK 2018; 2018: 18867.
[http://dx.doi.org/10.1038/s41598-017-18867-w]
[107]
Pusic KM, Pusic AD, Kraig RP. Environmental enrichment stimulates immune cell secretion of exosomes that promote CNS myelination and may regulate inflammation. Cell Mol Neurobiol 2016; 36(3): 313-25.
[http://dx.doi.org/10.1007/s10571-015-0269-4] [PMID: 26993508]
[108]
Ren ZW, Zhou JG, Xiong ZK, Zhu FZ, Guo XD. Effect of exosomes derived from MiR-133b-modified ADSCs on the recovery of neuro-logical function after SCI. Eur Rev Med Pharmaco 2019; 23(1): 52-60.
[PMID: 30657546]
[109]
Xin H, Li Y, Liu Z, et al. MiR-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesen-chymal stromal cells in rats via transfer of exosome-enriched extracellular particles. Stem Cells 2013; 31(12): 2737-46.
[http://dx.doi.org/10.1002/stem.1409] [PMID: 23630198]
[110]
Yuji S. Takeda, Xu Q. Neuronal differentiation of human mesenchymal stem cells using exosomes derived from differentiating neuronal cells. PLoS One 2015; 8(10): e135111.
[111]
Wang Y, Lai X, Wu D, Liu B, Wang N, Rong L. Umbilical mesenchymal stem cell-derived exosomes facilitate spinal cord functional re-covery through the miR-199a-3p/145-5p-mediated NGF/TrkA signaling pathway in rats. Stem Cell Res Ther 2021; 12(1): 117.
[http://dx.doi.org/10.1186/s13287-021-02148-5] [PMID: 33579361]
[112]
Tassew NG, Charish J, Shabanzadeh AP, et al. Exosomes mediate mobilization of autocrine wnt10b to promote axonal regeneration in the injured CNS. Cell Rep 2017; 20(1): 99-111.
[http://dx.doi.org/10.1016/j.celrep.2017.06.009] [PMID: 28683327]
[113]
Wei Z, Fan B, Ding H, et al. Proteomics analysis of Schwann cell-derived exosomes: A novel therapeutic strategy for central nervous sys-tem injury. Mol Cell Biochem 2019; 457(1-2): 51-9.
[http://dx.doi.org/10.1007/s11010-019-03511-0] [PMID: 30830528]
[114]
Komaki M, Numata Y, Morioka C, et al. Exosomes of human placenta-derived mesenchymal stem cells stimulate angiogenesis. Stem Cell Res Ther 2017; 8(1): 219.
[http://dx.doi.org/10.1186/s13287-017-0660-9] [PMID: 28974256]
[115]
Han Y, Ren J, Bai Y, Pei X, Han Y. Exosomes from hypoxia-treated human adipose-derived mesenchymal stem cells enhance angiogene-sis through VEGF/VEGF-R. Int J Biochem Cell Biol 2019; 109(109): 59-68.
[http://dx.doi.org/10.1016/j.biocel.2019.01.017] [PMID: 30710751]
[116]
Gonzalez-King H, García NA, Oviedo IO, et al. Hypoxia inducible Factor-1 alpha potentiates Jagged 1-mediated angiogenesis by mesen-chymal stem cell-derived exosomes. Stem Cells 2017; 7(35): 1747-59.
[117]
Chen CY, Rao SS, Ren L, et al. Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis. Theranostics 2018; 8(6): 1607-23.
[http://dx.doi.org/10.7150/thno.22958] [PMID: 29556344]
[118]
Cao Y, Xu Y, Chen C, Xie H, Lu H, Hu J. Local delivery of USC-derived exosomes harboring ANGPTL3 enhances spinal cord functional recovery after injury by promoting angiogenesis. Stem Cell Res Ther 2021; 12(1): 20.
[http://dx.doi.org/10.1186/s13287-020-02078-8] [PMID: 33413639]
[119]
Gong M, Yu B, Wang J, et al. Mesenchymal stem cells release exosomes that transfer miRNAs to endothelial cells and promote angiogene-sis. Oncotarget 2017; 8(28): 45200-12.
[http://dx.doi.org/10.18632/oncotarget.16778] [PMID: 28423355]
[120]
An Y, Zhao J, Nie F, et al. Exosomes from Adipose-Derived Stem Cells (ADSCs) overexpressing miR-21 promote vascularization of endothelial cells. Sci Rep-UK 2019; 9(1)
[121]
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): 2182-9.
[http://dx.doi.org/10.1242/jcs.170373] [PMID: 27252357]
[122]
Che P, Liu J, Shan Z, et al. miR-125a-5p impairs endothelial cell angiogenesis in aging mice via RTEF-1 downregulation. Aging Cell 2014; 13(5): 926-34.
[http://dx.doi.org/10.1111/acel.12252] [PMID: 25059272]
[123]
Lu Y, Zhou Y, Zhang R, et al. Bone mesenchymal stem cell-derived extracellular vesicles promote recovery following spinal cord injury via improvement of the integrity of the blood-spinal cord barrier. Front Neurosci 2019; 13: 209.
[http://dx.doi.org/10.3389/fnins.2019.00209] [PMID: 30914918]
[124]
Yuan X, Wu Q, Wang P, et al. Exosomes derived from pericytes improve microcirculation and protect blood-spinal cord barrier after spinal cord injury in mice. Front Neurosci 2019; 13: 319.
[http://dx.doi.org/10.3389/fnins.2019.00319] [PMID: 31040762]
[125]
Ding SQ, Chen J, Wang SN, et al. Identification of serum exosomal microRNAs in acute spinal cord injured rats. Exp Biol Med (Maywood) 2019; 244(14): 1149-61.
[http://dx.doi.org/10.1177/1535370219872759] [PMID: 31450959]
[126]
Kerr N, García-Contreras M, Abbassi S, et al. Inflammasome proteins in serum and serum-derived extracellular vesicles as biomarkers of stroke. Front Mol Neurosci 2018; 11: 309.
[http://dx.doi.org/10.3389/fnmol.2018.00309] [PMID: 30233311]

Rights & Permissions Print Cite
Article Metrics
16
1
© 2024 Bentham Science Publishers | Privacy Policy