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.
Graphical Abstract
[PMID: 25278785]
[http://dx.doi.org/10.1037/emo0000055] [PMID: 26053247]
[http://dx.doi.org/10.1007/s12035-017-0858-y] [PMID: 29307082]
[http://dx.doi.org/10.1007/s00345-018-2301-z] [PMID: 29752515]
[PMID: 625429]
[http://dx.doi.org/10.1016/j.neuint.2016.04.011] [PMID: 27131734]
[http://dx.doi.org/10.1159/000491469] [PMID: 29969758]
[http://dx.doi.org/10.1007/s10735-017-9711-x] [PMID: 28229263]
[http://dx.doi.org/10.1523/JNEUROSCI.1339-15.2015] [PMID: 26609164]
[http://dx.doi.org/10.1016/j.biopha.2019.108818] [PMID: 31102912]
[http://dx.doi.org/10.1073/pnas.1902513116] [PMID: 31320591]
[http://dx.doi.org/10.1016/j.tins.2021.01.003] [PMID: 33581883]
[http://dx.doi.org/10.3390/cells10081872] [PMID: 34440641]
[http://dx.doi.org/10.3389/fnmol.2019.00081] [PMID: 31031590]
[http://dx.doi.org/10.1186/s12974-018-1268-4] [PMID: 30107848]
[http://dx.doi.org/10.1016/j.neuroscience.2018.12.005] [PMID: 30553796]
[http://dx.doi.org/10.1016/j.athoracsur.2017.12.014] [PMID: 29337123]
[http://dx.doi.org/10.1007/s13311-018-0629-0] [PMID: 29728851]
[http://dx.doi.org/10.1016/0005-2736(81)90512-5] [PMID: 6266476]
[http://dx.doi.org/10.1007/978-981-10-4397-0_1] [PMID: 28936729]
[http://dx.doi.org/10.1083/jcb.101.3.942] [PMID: 2993317]
[http://dx.doi.org/10.1083/jcb.97.2.329] [PMID: 6309857]
[http://dx.doi.org/10.1038/nrm.2017.125] [PMID: 29339798]
[http://dx.doi.org/10.1016/j.cub.2018.01.059] [PMID: 29689228]
[http://dx.doi.org/10.1038/nri855] [PMID: 12154376]
[http://dx.doi.org/10.1038/s41467-018-06197-y] [PMID: 30258067]
[http://dx.doi.org/10.1053/gast.2001.26263] [PMID: 11487543]
[http://dx.doi.org/10.1016/j.devcel.2006.01.012] [PMID: 16516837]
[http://dx.doi.org/10.1038/ncb2502] [PMID: 22660413]
[http://dx.doi.org/10.1016/j.semcdb.2017.08.022] [PMID: 28807885]
[http://dx.doi.org/10.3390/cancers11060888] [PMID: 31242686]
[http://dx.doi.org/10.3389/fonc.2021.675940] [PMID: 34094979]
[http://dx.doi.org/10.1146/annurev-physiol-021014-071641] [PMID: 25293529]
[http://dx.doi.org/10.1083/jcb.201211138] [PMID: 23420871]
[http://dx.doi.org/10.1074/jbc.M112.446831] [PMID: 23439645]
[http://dx.doi.org/10.1038/ncomms3980] [PMID: 24356509]
[http://dx.doi.org/10.1016/j.gpb.2015.02.001] [PMID: 25724326]
[http://dx.doi.org/10.1016/j.celrep.2014.07.035] [PMID: 25159140]
[http://dx.doi.org/10.1016/j.celrep.2014.08.027] [PMID: 25242326]
[http://dx.doi.org/10.3390/ijms19124124] [PMID: 30572617]
[http://dx.doi.org/10.1016/j.neulet.2019.134480] [PMID: 31493550]
[http://dx.doi.org/10.7150/thno.30879] [PMID: 31244932]
[http://dx.doi.org/10.1096/fj.201700673r] [PMID: 28935818]
[http://dx.doi.org/10.1038/nn.4132] [PMID: 26436904]
[http://dx.doi.org/10.1016/j.neures.2019.07.007] [PMID: 31348996]
[http://dx.doi.org/10.1002/dneu.20559] [PMID: 17701989]
[http://dx.doi.org/10.1073/pnas.1013793107] [PMID: 21148774]
[http://dx.doi.org/10.3389/fncel.2013.00251] [PMID: 24368897]
[http://dx.doi.org/10.1038/s41556-018-0039-x] [PMID: 29434374]
[http://dx.doi.org/10.1016/j.nbd.2017.12.016] [PMID: 29274429]
[http://dx.doi.org/10.1371/journal.pbio.3000621] [PMID: 33351792]
[http://dx.doi.org/10.1172/JCI90608] [PMID: 28737515]
[http://dx.doi.org/10.1038/s41419-019-1571-8] [PMID: 31000697]
[http://dx.doi.org/10.3390/jcm8010023] [PMID: 30585207]
[http://dx.doi.org/10.1016/j.cell.2012.05.012] [PMID: 22682243]
[http://dx.doi.org/10.1126/scisignal.135re9] [PMID: 18765832]
[http://dx.doi.org/10.1177/0963689719870999] [PMID: 31423807]
[http://dx.doi.org/10.1016/j.yjmcc.2018.04.012] [PMID: 29698635]
[http://dx.doi.org/10.1016/j.neures.2017.05.003] [PMID: 28522336]
[http://dx.doi.org/10.1182/blood-2013-12-544445] [PMID: 26232171]
[http://dx.doi.org/10.1080/21691401.2020.1725031] [PMID: 32054316]
[http://dx.doi.org/10.1038/s41434-019-0101-8] [PMID: 31570818]
[http://dx.doi.org/10.1523/JNEUROSCI.0150-08.2008] [PMID: 18614687]
[http://dx.doi.org/10.1002/jcp.27690] [PMID: 30387159]
[http://dx.doi.org/10.1002/jcp.29253] [PMID: 31583718]
[http://dx.doi.org/10.1186/s12951-020-00630-5] [PMID: 32404105]
[http://dx.doi.org/10.3389/fnins.2018.00845] [PMID: 30524227]
[http://dx.doi.org/10.1016/j.neuroscience.2019.10.043] [PMID: 31704348]
[PMID: 32223487]
[http://dx.doi.org/10.1186/s13287-021-02401-x] [PMID: 34112262]
[http://dx.doi.org/10.1016/j.actbio.2021.03.018] [PMID: 33722788]
[http://dx.doi.org/10.1007/s11064-019-02950-x] [PMID: 31953741]
[http://dx.doi.org/10.1007/s12031-019-01437-2] [PMID: 31768946]
[http://dx.doi.org/10.1007/s11011-020-00563-w] [PMID: 32185593]
[http://dx.doi.org/10.1080/13813455.2019.1691601] [PMID: 32141339]
[http://dx.doi.org/10.3390/ijms18071413] [PMID: 28671586]
[http://dx.doi.org/10.18632/aging.102283] [PMID: 31563124]
[http://dx.doi.org/10.3389/fimmu.2021.663726] [PMID: 34135893]
[http://dx.doi.org/10.2147/DDDT.S209636] [PMID: 31695336]
[http://dx.doi.org/10.1016/j.msec.2018.04.006] [PMID: 29752089]
[http://dx.doi.org/10.1016/j.brainresbull.2021.02.015] [PMID: 33609602]
[http://dx.doi.org/10.1186/s13075-020-2146-x] [PMID: 32272965]
[http://dx.doi.org/10.1016/j.redox.2021.101932] [PMID: 33714739]
[http://dx.doi.org/10.1016/j.jtcvs.2018.07.095] [PMID: 30224076]
[http://dx.doi.org/10.18632/aging.102568] [PMID: 31848325]
[http://dx.doi.org/10.1089/neu.2017.5049] [PMID: 29149810]
[http://dx.doi.org/10.1038/nature17623] [PMID: 27027288]
[http://dx.doi.org/10.1007/s00401-009-0619-8] [PMID: 20012068]
[http://dx.doi.org/10.1089/neu.2018.5835] [PMID: 29848167]
[http://dx.doi.org/10.1021/acsnano.9b01892] [PMID: 31454225]
[http://dx.doi.org/10.1159/000494652] [PMID: 30376671]
[http://dx.doi.org/10.3389/fneur.2019.01225] [PMID: 31849808]
[http://dx.doi.org/10.1038/s41467-019-11534-w] [PMID: 31511506]
[http://dx.doi.org/10.4103/1673-5374.143423] [PMID: 25422640]
[http://dx.doi.org/10.1186/s12974-015-0270-3] [PMID: 25889216]
[http://dx.doi.org/10.1186/s12974-020-1726-7] [PMID: 32019561]
[http://dx.doi.org/10.1007/s10735-020-09950-0] [PMID: 33548000]
[http://dx.doi.org/10.1007/s10753-020-01230-z] [PMID: 32307615]
[http://dx.doi.org/10.1038/s41598-017-18867-w]
[http://dx.doi.org/10.1007/s10571-015-0269-4] [PMID: 26993508]
[PMID: 30657546]
[http://dx.doi.org/10.1002/stem.1409] [PMID: 23630198]
[http://dx.doi.org/10.1186/s13287-021-02148-5] [PMID: 33579361]
[http://dx.doi.org/10.1016/j.celrep.2017.06.009] [PMID: 28683327]
[http://dx.doi.org/10.1007/s11010-019-03511-0] [PMID: 30830528]
[http://dx.doi.org/10.1186/s13287-017-0660-9] [PMID: 28974256]
[http://dx.doi.org/10.1016/j.biocel.2019.01.017] [PMID: 30710751]
[http://dx.doi.org/10.7150/thno.22958] [PMID: 29556344]
[http://dx.doi.org/10.1186/s13287-020-02078-8] [PMID: 33413639]
[http://dx.doi.org/10.18632/oncotarget.16778] [PMID: 28423355]
[http://dx.doi.org/10.1242/jcs.170373] [PMID: 27252357]
[http://dx.doi.org/10.1111/acel.12252] [PMID: 25059272]
[http://dx.doi.org/10.3389/fnins.2019.00209] [PMID: 30914918]
[http://dx.doi.org/10.3389/fnins.2019.00319] [PMID: 31040762]
[http://dx.doi.org/10.1177/1535370219872759] [PMID: 31450959]
[http://dx.doi.org/10.3389/fnmol.2018.00309] [PMID: 30233311]