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
Review Article

Regenerative Potential of Stem Cell-derived Extracellular Vesicles in Spinal Cord Injury (SCI)

Author(s): Franklin J. Herbert, Dhivya Bharathi, Sevanthy Suresh, Ernest David and Sanjay Kumar*

Volume 17, Issue 3, 2022

Published on: 20 December, 2021

Page: [280 - 293] Pages: 14

DOI: 10.2174/1574888X16666210923113658

Price: $65

Abstract

Spinal cord injury is a devastating condition that is critically challenging and progressive, needing immediate medical attention due to its complex pathophysiology and affecting the social status and economic burden. Stem cell therapy has been the emerging therapeutic trend to treat various diseases for decades. Mesenchymal stem cells pose more advantages over other stem cells in immune-modulation, immune evasiveness, self-renewal, multipotency, etc. Due to various issues in the recent past related to allogenic transplants, ethical concerns in obtaining tissues and adult cells, host immune response, GMP grade production and certification, cell-derived products or cell secretome have proven to be a promising approach and have been implicated in many studies and also in many clinical trials. Utilization of these human MSC-derived exosomes/extracellular vesicles in spinal cord injury has also been demonstrated in many pre-clinical animal models. It is now proven to be therapeutically more efficient and safer than cell therapy. This review focuses on employing human MSC derived EVs for SCI and continues to elucidate the recent advances and emerging EVs trends from other cell types. We discuss biomaterial-based synergistic intervention, mention mimetics and nanovesicles and finally touch upon safety concerns in EV therapy.

Keywords: Extracellular vesicles, exosomes, mesenchymal stem cells, apoptosis, inflammation, spinal cord injury, autophagy, stem cells, neuroprotection, angiogenesis, motor recovery.

« Previous Next »
[1]
Oyinbo CA. Secondary injury mechanisms in traumatic spinal cord injury: A nugget of this multiply cascade. Acta Neurobiol Exp 2011; 71(2): 281-99.
[PMID: 21731081]
[2]
Mehta S, McIntyre A, Janzen S, Loh E. Systematic review of pharmacologic treatments of pain after spinal cord injury: An update. Elsevier 2016. Available from: https://www.sciencedirect.com/science/article/pii/S0003999316000113
[3]
Gao L, Peng Y, Xu W, He P, Li T, Lu X. Progress in stem cell therapy for spinal cord injury. Stem Cells Int 2020; 2020
[http://dx.doi.org/10.1155/2020/2853650]
[4]
Cofano F, Boido M, Monticelli M, Zenga F, Ducati A, Vercelli A. Mesenchymal stem cells for spinal cord injury: Current options limitations, and future of cell therapy. Int J Mol Sci 2019; 20(11): 2698.
[5]
Liau LL, Looi QH, Chia WC, Subramaniam T, Ng MH, Law JX. Treatment of spinal cord injury with mesenchymal stem cells. Cell Biosci 2020; 10(1): 112.
[http://dx.doi.org/10.1186/s13578-020-00475-3] [PMID: 32983406]
[6]
Sabapathy V, Sundaram B, v M S, Mankuzhy P, Kumar S. Human Wharton’s jelly mesenchymal stem cells plasticity augments scar-free skin wound healing with hair growth. PLoS One 2014; 9(4): e93726.
[http://dx.doi.org/10.1371/journal.pone.0093726] [PMID: 24736473]
[7]
Caby MP, Lankar D, Vincendeau-Scherrer C, Raposo G, Bonnerot C. Exosomal-like vesicles are present in human blood plasma. Int Immunol 2005; 17(7): 879-87.
[http://dx.doi.org/10.1093/intimm/dxh267] [PMID: 15908444]
[8]
Pisitkun T, Shen RF, Knepper MA. Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci USA 2004; 101(36): 13368-73.
[http://dx.doi.org/10.1073/pnas.0403453101]
[9]
Vojtech L, Woo S, Hughes S, et al. Exosomes in human semen carry a distinctive repertoire of small non-coding RNAs with potential regulatory functions. Nuc Acids Res 2014; 42(11): 7290-304.
[http://dx.doi.org/10.1093/nar/gku347] [PMID: 24838567]
[10]
Zlotogorski-Hurvitz A, Dayan D, Chaushu G, et al. Human saliva-derived exosomes: comparing methods of isolation. J Histochem Cytochem 2015; 63(3): 181-9.
[http://dx.doi.org/10.1369/0022155414564219] [PMID: 25473095]
[11]
Yuan Z, Bedi B, Sadikot RT. Bronchoalveolar lavage exosomes in lipopolysaccharide-induced septic lung injury. J Vis Exp 2018; 21(135): 57737.
[http://dx.doi.org/10.3791/57737] [PMID: 29863671]
[12]
Akers JC, Ramakrishnan V, Kim R, et al. MiR-21 in the extracellular vesicles (EVs) of cerebrospinal fluid (CSF): A platform for glioblastoma biomarker development. PLoS One 2013; 8(10): e78115.
[http://dx.doi.org/10.1371/journal.pone.0078115] [PMID: 24205116]
[13]
Hornick NI, Huan J, Doron B, et al. Serum Exosome MicroRNA as a minimally-invasive early biomarker of AML. Sci Rep 2015; 5(1): 1-2.
[http://dx.doi.org/10.1038/srep11295] [PMID: 26067326]
[14]
Dixon CL, Sheller-Miller S, Saade GR, et al. Amniotic fluid exosome proteomic profile exhibits unique pathways of term and preterm labor. Endocrinology 2018; 159(5): 2229-40.
[http://dx.doi.org/10.1210/en.2018-00073] [PMID: 29635386]
[15]
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.
[16]
Grigor’eva AE, Tamkovich SN, Eremina AV, Tupikin AE, Kabilov MR, Chernykh VV. Characteristics of exosomes andmicroparticles discovered in human tears. Biomeditsinskaya Khimiya 2016; 62(1): 99-106.
[http://dx.doi.org/10.18097/PBMC20166201099]
[17]
Milasan A, Tessandier N, Tan S, Brisson A, Boilard E, Martel C. Extracellular vesicles are present in mouse lymph and their level differs in atherosclerosis. J Extracell Vesicles 2016; 5: 31427.
[18]
Yoon SB, Chang JH. Extracellular vesicles in bile: A game changer in the diagnosis of indeterminate biliary stenoses? Hepatobiliary Surg Nutr 2017; 6(6): 408-10.
[http://dx.doi.org/10.21037/hbsn.2017.10.01] [PMID: 29312977]
[19]
Yoshida Y, Yamamoto H, Morita R, et al. Detection of DNA methylation of gastric juice-derived exosomes in gastric cancer. Integrat Mol Med 2014; 1: 17-21.
[http://dx.doi.org/10.15761/IMM.1000105]
[20]
Rezaie J, Ajezi S, Avci B, et al. Exosomes and their application in biomedical field: Difficulties and advantages. Mol Neurobiol 2018; 55(4): 3372-93.
[21]
Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science 2020; 367(6478): eaau6977.
[22]
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.
[23]
Doyle L, Wang M. Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis. Cells 2019; 8(7): 727.
[24]
Smith ZJ, Lee C, Rojalin T, et al. Single exosome study reveals subpopulations distributed among cell lines with variability related to membrane content. J Extracell Vesicles 2015; 4(1): 28533.
[http://dx.doi.org/10.3402/jev.v4.28533] [PMID: 26649679]
[25]
Laulagnier K, Vincent-Schneider H, Hamdi S, Subra C, Lankar D, Record M. Characterization of exosome subpopulations from RBL-2H3 cells using fluorescent lipids. Blood Cells Mol Dis 2005; 35(2): 116-21.
[http://dx.doi.org/10.1016/j.bcmd.2005.05.010] [PMID: 16023874]
[26]
Varderidou-Minasian S, Lorenowicz MJ. Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: Challenges and opportunities. Theranostics 2020; 10(13): 5979-97.
[27]
Gurunathan S, Kang M-H, Jeyaraj M, Qasim M, Kim J-H. Review of the isolation, characterization, biological function, and multifarious therapeutic approaches of exosomes. Cells 2019; 8(4): 307.
[28]
Théry C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles 2018; 7(1): 1535750.
[http://dx.doi.org/10.1080/20013078.2018.1535750] [PMID: 30637094]
[29]
Khan N, Cao T, He J, Ritzel RM, Li Y, Rebecca J. Spinal cord injury alters microRNA and CD81+ exosome levels in plasma extracellular nanoparticles with neuroinflammatory potential. Brain Behav Immun 2021; 92: 165-83.
[http://dx.doi.org/10.1016/j.bbi.2020.12.007] [PMID: 33307173]
[30]
Ditor DS, John S, Cakiroglu J, Kittmer C, Foster PJ, Weaver LC. Magnetic resonance imaging versus histological assessment for estimation of lesion volume after experimental spinal cord injury. Laboratory investigation. J Neurosurg Spine 2008; 9(3): 301-6.
[http://dx.doi.org/10.3171/SPI/2008/9/9/301] [PMID: 18928229]
[31]
Orr MB, Gensel JC. Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses. Springer New York 2018; 15(3): 541-53.
[http://dx.doi.org/10.1007/s13311-018-0631-6] [PMID: 29717413]
[32]
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]
[33]
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(89): 194-204.
[http://dx.doi.org/10.1016/j.msec.2018.04.006] [PMID: 29752089]
[34]
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): e0190358.
[http://dx.doi.org/10.1371/journal.pone.0190358] [PMID: 29293592]
[35]
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]
[36]
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]
[37]
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]
[38]
Huang JH, Xu Y, Yin XM, Lin FY. Exosomes derived from miR-126-modified MSCs promote angiogenesis and neurogenesis and attenuate 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]
[39]
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]
[40]
Huang JH, Yin XM, Xu Y, et al. Systemic administration of exosomes released from mesenchymal stromal cells attenuates apoptosis, inflammation, and promotes angiogenesis after spinal cord injury in rats. J Neurotrauma 2017; 34(24): 3388-96.
[http://dx.doi.org/10.1089/neu.2017.5063] [PMID: 28665182]
[41]
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]
[42]
Ruppert KA, Nguyen TT, Prabhakara KS, et al. Human mesenchymal stromal cell-derived extracellular vesicles modify microglial response 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]
[43]
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]
[44]
Noori L, Arabzadeh S, Mohamadi Y, Mojaverrostami S, Mokhtari T, Akbari M. Intrathecal administration of the extracellular vesicles derived from human Wharton’s jelly stem cells inhibit inflammation and attenuate the activity of inflammasome complexes after spinal cord injury in rats. Neurosci Res 2021; 170: 87-98.
[http://dx.doi.org/10.1016/j.neures.2020.07.011] [PMID: 32717259]
[45]
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 neurons in patients with spinal cord injury. J Cell Physiol 2019; 234(7): 10205-17.
[http://dx.doi.org/10.1002/jcp.27690] [PMID: 30387159]
[46]
Ji W, Jiang W, Li M, Li J, Li Z. miR-21 deficiency contributes to the impaired protective effects of obese rat mesenchymal stem cell-derived exosomes against spinal cord injury. Biochimie 2019; 167: 171-8.
[http://dx.doi.org/10.1016/j.biochi.2019.10.002] [PMID: 31605737]
[47]
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]
[48]
Ren ZW, Zhou JG, Xiong ZK, Zhu FZ, Guo XD. Effect of exosomes derived from MiR-133b-modified ADSCs on the recovery of neurological function after SCI. Eur Rev Med Pharmacol Sci 2019; 23(1): 52-60.
[PMID: 30657546]
[49]
Yu T, Zhao C, Hou S, Zhou W, Wang B, Chen Y. Exosomes secreted from miRNA-29b-modified mesenchymal stem cells repaired spinal cord injury in rats. Braz J Med Biol Res 2019; 52(12): e8735.
[http://dx.doi.org/10.1590/1414-431x20198735] [PMID: 31826179]
[50]
Luo Y, Xu T, Liu W, Rong Y, Wang J, Fan J. 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.
[http://dx.doi.org/10.1080/00207454.2020.1734598] [PMID: 32223487]
[51]
Li C, Li X, Zhao B, Wang C. Exosomes derived from miR-544- modified mesenchymal stem cells promote recovery after spinal cord injury. Arch Physiol Biochem 2020; 126(4): 369-75.
[http://dx.doi.org/10.1080/13813455.2019.1691601] [PMID: 32141339]
[52]
Luo Z, Wu F, Xue E, et al. Hypoxia preconditioning promotes bone marrow mesenchymal stem cells survival by inducing HIF-1α in injured neuronal cells derived exosomes culture system. Cell Death Dis 2019; 10(2): 134.
[http://dx.doi.org/10.1038/s41419-019-1410-y] [PMID: 30755595]
[53]
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]
[54]
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]
[55]
Zhou X, Chu X, Yuan H, et al. Mesenchymal stem cell derived EVs mediate neuroprotection after spinal cord injury in rats via the microRNA-21-5p/FasL gene axis. Biomed Pharmacother 2019; 115: 108818.
[http://dx.doi.org/10.1016/j.biopha.2019.108818] [PMID: 31102912]
[56]
Kim HY, Kumar H, Jo MJ, et al. Therapeutic efficacy-potentiated and diseased organ-targeting nanovesicles derived from mesenchymal stem cells for spinal cord injury treatment. Nano Lett 2018; 18(8): 4965-75.
[http://dx.doi.org/10.1021/acs.nanolett.8b01816] [PMID: 29995418]
[57]
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]
[58]
Wang H, Zheng Z, Han W, et al. Metformin promotes axon regeneration after spinal cord injury through inhibiting oxidative stress and stabilizing microtubule. Oxid Med Cell Longev 2020; 2020: 9741369.
[http://dx.doi.org/10.1155/2020/9741369] [PMID: 31998447]
[59]
Zhang L, Zhang W, Zheng B, Tian N. Sinomenine attenuates traumatic spinal cord injury by suppressing oxidative stress and inflammation via Nrf2 pathway. Neurochem Res 2019; 44(4): 763-75.
[http://dx.doi.org/10.1007/s11064-018-02706-z] [PMID: 30603983]
[60]
Davies MJ. Protein oxidation and peroxidation. Biochem J 2016; 473(7): 805-25.
[http://dx.doi.org/10.1042/BJ20151227] [PMID: 27026395]
[61]
Ayala A, Muñoz MF, Argüelles S. Lipid eroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014; 2014: 360438.
[62]
Visavadiya NP, Patel SP, VanRooyen JL, Sullivan PG, Rabchevsky AG. Cellular and subcellular oxidative stress parameters following severe spinal cord injury. Redox Biol 2016; 8: 59-67.
[http://dx.doi.org/10.1016/j.redox.2015.12.011] [PMID: 26760911]
[63]
Niu Y, Xia X, Song P, et al. Bone mesenchymal stem cell-conditioned medium attenuates the effect of oxidative stress injury on NSCs by inhibiting the Notch1 signaling pathway. Cell Biol Int 2019; 43(11): 1267-75.
[http://dx.doi.org/10.1002/cbin.11126] [PMID: 30839137]
[64]
Yeng C-HH, Chen P-JJ, Chang H-KK, et al. Attenuating spinal cord injury by conditioned medium from human umbilical cord blood-derived CD34+ cells in rats. Taiwan J Obstet Gynecol 2016; 55(1): 85-93.
[http://dx.doi.org/10.1016/j.tjog.2015.12.009] [PMID: 26927256]
[65]
Zhong D, Cao Y, Li CJ, et al. Neural stem cell-derived exosomes facilitate spinal cord functional recovery after injury by promoting angiogenesis. Exp Biol Med 2020; 245(1): 54-65.
[http://dx.doi.org/10.1177/1535370219895491] [PMID: 31903774]
[66]
Xue C, Shen Y, Li X, et al. Exosomes derived from hypoxia-treated human adipose mesenchymal stem cells enhance angiogenesis through the PKA signaling pathway. Stem Cells Dev 2018; 27(7): 456-65.
[http://dx.doi.org/10.1089/scd.2017.0296] [PMID: 29415626]
[67]
Lee JR, Kyung JW, Kumar H, et al. Targeted delivery of mesenchymal stem cell-derived nanovesicles for spinal cord injury treatment. Int J Mol Sci 2020; 21(11): 1-20.
[http://dx.doi.org/10.3390/ijms21114185] [PMID: 32545361]
[68]
Wood CR, Al Delfi IRT, Innes JF, Myint P, Johnson WEB. Exposing mesenchymal stem cells to chondroitin sulphated proteoglycans reduces their angiogenic and neuro-adhesive paracrine activity. Biochimie 2018; 155: 26-36.
[http://dx.doi.org/10.1016/j.biochi.2018.04.011] [PMID: 29680669]
[69]
Orekhov AN, Bobryshev YV, Chistiakov DA. The complexity of cell composition of the intima of large arteries: focus on pericyte- like cells. Cardiovasc Res 2014; 103(4): 438-51.
[http://dx.doi.org/10.1093/cvr/cvu168] [PMID: 25016615]
[70]
Bergers G, Song S. The role of pericytes in blood-vessel formation and maintenance Neuro Oncology 2005; 7(4): 452-64.
[71]
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]
[72]
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]
[73]
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]
[74]
Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms. J Pathol 2010; 221(1): 3-12.
[http://dx.doi.org/10.1002/path.2697] [PMID: 20225336]
[75]
Tsai M-J, Liou D-Y, Lin Y-R, 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]
[76]
Gu J, Jin ZS, Wang CM, Yan XF, Mao YQ, Chen S. Bone marrow mesenchymal stem cell-derived exosomes improves spinal cord function after injury in rats by activating autophagy. Drug Des Devel Ther 2020; 14: 1621-31.
[http://dx.doi.org/10.2147/DDDT.S237502] [PMID: 32425507]
[77]
Rong Y, Liu W, Wang J, et al. Neural stem cell-derived small extracellular vesicles attenuate apoptosis and neuroinflammation after traumatic 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]
[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]
Huang JH, Fu CH, Xu Y, Yin XM, 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]
[80]
Munter JP, Beugels J, Munter S, et al. Standardized human bone marrow-derived stem cells infusion improves survival and recovery in a rat model of spinal cord injury. J Neurol Sci 2019; 402: 16-29.
[http://dx.doi.org/10.1016/j.jns.2019.05.002] [PMID: 31100652]
[81]
Ma K, Xu H, Zhang J, Zhao F, Liang H, Sun H. 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 2019; 11(24): 12278-94.
[82]
Chudickova M, Vackova I, Machova Urdzikova L, et al. The effect of Wharton jelly-derived mesenchymal stromal cells and their conditioned media in the treatment of a rat spinal cord injury. Int J Mol Sci 2019; 20(18): E4516.
[http://dx.doi.org/10.3390/ijms20184516] [PMID: 31547264]
[83]
Li L, Zhang Y, Mu J, et al. Transplantation of human mesenchymal stem-cell-derived exosomes immobilized in an adhesive hydrogel for effective treatment of spinal cord injury. Nano Lett 2020; 20(6): 4298-305.
[http://dx.doi.org/10.1021/acs.nanolett.0c00929] [PMID: 32379461]
[84]
Kim DK, 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]
[85]
Beattie MS, Farooqui AA, Bresnahan JC. Review of current evidence for apoptosis after spinal cord injury. J Neurotrauma 2000; 17(10): 915-25.
[http://dx.doi.org/10.1089/neu.2000.17.915] [PMID: 11063057]
[86]
Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2002; 2(9): 647-56.
[http://dx.doi.org/10.1038/nrc883] [PMID: 12209154]
[87]
Anderson AJ, Robert S, Huang W, Young W, Cotman CW. Activation of complement pathways after contusion-induced spinal cord injury. J Neurotrauma 2004; 21(12): 1831-46.
[http://dx.doi.org/10.1089/neu.2004.21.1831] [PMID: 15684772]
[88]
Rebhun J, Madorsky JGB, Glovsky MM. Proteins of the complement system and acute phase reactants in sera of patients with spinal cord injury. Ann Allergy 1991; 66(4): 335-8.
[PMID: 1707599]
[89]
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]
[90]
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 Nanobiotechnology 2020; 18(1): 72.
[http://dx.doi.org/10.1186/s12951-020-00630-5] [PMID: 32404105]
[91]
Sekine Y, Lindborg JA, Strittmatter SM. A proteolytic C-terminal fragment of Nogo-A (reticulon-4A) is released in exosomes and potently inhibits axon regeneration. J Biol Chem 2020; 295(8): 2175-83.
[http://dx.doi.org/10.1074/jbc.RA119.009896] [PMID: 31748413]
[92]
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]
[93]
Fan Y, Li Y, Huang S, Xu H, Li H, Liu B. Resveratrol-primed exosomes strongly promote the recovery of motor function in SCI rats by activating autophagy and inhibiting apoptosis via the PI3K signaling pathway. Neurosci Lett 2020; 736: 135262.
[http://dx.doi.org/10.1016/j.neulet.2020.135262] [PMID: 32682847]
[94]
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.
[http://dx.doi.org/10.1002/glia.23566] [PMID: 30485542]
[95]
Goncalves MB, Wu Y, Clarke E, et al. Regulation of myelination by exosome associated retinoic acid release from NG2-positive cells. J Neurosci 2019; 39(16): 3013-27.
[http://dx.doi.org/10.1523/JNEUROSCI.2922-18.2019] [PMID: 30760627]
[96]
de Rivero Vaccari JP, Brand F III, Adamczak S, et al. Exosome- mediated inflammasome signaling after central nervous system injury. J Neurochem 2016; 136(Suppl. 1): 39-48.
[http://dx.doi.org/10.1111/jnc.13036] [PMID: 25628216]
[97]
Jiang D, Gong F, Ge X, et al. Neuron-derived exosomes-transmitted miR-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytes. J Nanobiotechnology 2020; 18(1): 105.
[http://dx.doi.org/10.1186/s12951-020-00665-8] [PMID: 32711535]
[98]
Rong Y, Liu W, Lv C, et al. Neural stem cell small extracellular vesicle-based delivery of 14-3-3t reduces apoptosis and neuroinflammation following traumatic spinal cord injury by enhancing autophagy by targeting Beclin-1. Aging 2019; 11(18): 7723-45.
[http://dx.doi.org/10.18632/aging.102283] [PMID: 31563124]
[99]
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]
[100]
Sundelacruz S, Kaplan DL. Stem cell- and scaffold-based tissue engineering approaches to osteochondral regenerative medicine. Semin Cell Dev Biol 2009; 20(6): 646-55.
[101]
Hsu JM, Shiue SJ, Yang KD, et al. Locally applied stem cell exosome-scaffold attenuates nerve injury-induced pain in rats. J Pain Res 2020; 13: 3257-68.
[http://dx.doi.org/10.2147/JPR.S286771] [PMID: 33304105]
[102]
Zhang J, Liu X, Li H, et al. Exosomes/tricalcium phosphate combination scaffolds can enhance bone regeneration by activating the PI3K/Akt signaling pathway. Stem Cell Res Ther 2016; 7(1): 136.
[http://dx.doi.org/10.1186/s13287-016-0391-3] [PMID: 27650895]
[103]
Jang SC, Gho YS. Could bioengineered exosome-mimetic nanovesicles be an efficient strategy for the delivery of chemotherapeutics? Nanomedicine 2014; 9(2): 177-80.
[http://dx.doi.org/10.2217/nnm.13.206] [PMID: 24552557]
[104]
Liang Y, Duan L, Xu X, Li X, Liu M, Chen H. Mesenchymal stem cell-derived exosomes for treatment of autism spectrum disorder. ACS Appl Bio Mater 2020; 3(9): 6384-93.
[http://dx.doi.org/10.1021/acsabm.0c00831]
[105]
Jung JW, Kwon M, Choi JC, et al. Familial occurrence of pulmonary embolism after intravenous, adipose tissue-derived stem cell therapy. Yonsei Med J 2013; 54(5): 1293-6.
[http://dx.doi.org/10.3349/ymj.2013.54.5.1293] [PMID: 23918585]
[106]
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]
[107]
Sabry D, Marzouk S, Zakaria R, Ibrahim HA, Samir M. The effect of exosomes derived from mesenchymal stem cells in the treatment of induced type 1 diabetes mellitus in rats. Biotechnol Lett 2020; 42(8): 1597-610.
[http://dx.doi.org/10.1007/s10529-020-02908-y] [PMID: 32430801]
[108]
Anjum A, Yazid MD, Fauzi Daud M, et al. Spinal cord injury: Pathophysiology, multimolecular interactions, and underlying recovery mechanisms. Int J Mol Sci 2020; 21(20): 1-35.
[http://dx.doi.org/10.3390/ijms21207533] [PMID: 33066029]
[109]
Heldring N, Mäger I, Wood MJA, Le Blanc K, Andaloussi SEL. Therapeutic potential of multipotent mesenchymal stromal cells and their extracellular vesicles. Hum Gene Ther 2015; 26(8): 506-17.
[http://dx.doi.org/10.1089/hum.2015.072] [PMID: 26153722]
[110]
Iraci N, Leonardi T, Gessler F, Vega B, Pluchino S. Focus on extracellular vesicles: Physiological role and signalling properties of extracellular membrane vesicles. Int J Mol Sci 2016; 17(2): 171.
[http://dx.doi.org/10.3390/ijms17020171] [PMID: 26861302]
[111]
Geffner LF, Santacruz P, Izurieta M, et al. Administration of autologous bone marrow stem cells into spinal cord injury patients via multiple routes is safe and improves their quality of life: comprehensive case studies. Cell Transplant 2008; 17(12): 1277-93.
[http://dx.doi.org/10.3727/096368908787648074] [PMID: 19364066]
[112]
Park HC, Shim YS, Ha Y, et al. Treatment of complete spinal cord injury patients by autologous bone marrow cell transplantation and administration of granulocyte-macrophage colony stimulating factor. Tissue Eng 2005; 11(5-6): 913-22.
[http://dx.doi.org/10.1089/ten.2005.11.913] [PMID: 15998231]
[113]
Syková E, Homola A, Mazanec R, et al. Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury. Cell Transplant 2006; 15(8-9): 675-87.
[http://dx.doi.org/10.3727/000000006783464381] [PMID: 17269439]
[114]
Bydon M, Dietz AB, Goncalves S, et al. CELLTOP Clinical Trial: First report from a phase 1 trial of autologous adipose tissue-derived mesenchymal stem cells in the treatment of paralysis due to traumatic spinal cord injury. Mayo Clin Proc 2020; 95(2): 406-14.
[http://dx.doi.org/10.1016/j.mayocp.2019.10.008] [PMID: 31785831]
[115]
Soria-Zavala K, García-Sánchez J, Rodríguez-Barrera R. Mesenchymal stem cells for clinical use after spinal cord injury. In: JJAI Arias, Ramos CAC, Eds. Paraplegia. UK: IntechOpen 2020.
[http://dx.doi.org/10.5772/intechopen.91839]
[116]
Willis GR, Kourembanas S, Mitsialis SA. Toward exosome-based therapeutics: Isolation, heterogeneity, and fit-for-purpose potency. Front Cardiovasc Med 2017; 4: 63.
[http://dx.doi.org/10.3389/fcvm.2017.00063] [PMID: 29062835]
[117]
Chen TS, Arslan F, Yin Y, et al. Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs. J Transl Med 2011; 9(1): 47.
[http://dx.doi.org/10.1186/1479-5876-9-47] [PMID: 21513579]
[118]
Watson DC, Bayik D, Srivatsan A, Bergamaschi C, Valentin A, Niu G. Efficient production and enhanced tumor delivery of engineered extracellular vesicles. Biomaterials 2016; 105: 195-205.
[http://dx.doi.org/10.1016/j.biomaterials.2016.07.003]
[119]
Jafari D, Malih S, Eini M, et al. Improvement, scaling-up, and downstream analysis of exosome production. Crit Rev Biotechnol 2020; 40(8): 1098-112.
[http://dx.doi.org/10.1080/07388551.2020.1805406] [PMID: 32772758]
[120]
Harmati M, Tarnai Z, Decsi G, et al. Stressors alter intercellular communication and exosome profile of nasopharyngeal carcinoma cells. J Oral Pathol Med 2017; 46(4): 259-66.
[http://dx.doi.org/10.1111/jop.12486] [PMID: 27598726]
[121]
Willms E, Cabañas C, Mäger I, Wood MJA, Vader P. Extracellular vesicle heterogeneity: Subpopulations, isolation techniques, and diverse functions in cancer progression. Frontiers Immunol 2018; 9: 738.
[122]
Zhang M, Jin K, Gao L, Zhang Z, Li F, Zhou F. Methods and technologies for exosome isolation and characterization. Small Methods 2018; 2(9): 1-10.
[http://dx.doi.org/10.1002/smtd.201800021]
[123]
Li P, Kaslan M, Lee SH, Yao J, Gao Z. Progress in exosome isolation techniques. Theranostics 2017; 7(3): 789-804.
[http://dx.doi.org/10.7150/thno.18133] [PMID: 28255367]
[124]
Yang D, Zhang W, Zhang H, et al. Progress, opportunity, and perspective on exosome isolation - efforts for efficient exosome-based theranostics. Theranostics 2020; 10(8): 3684-707.
[http://dx.doi.org/10.7150/thno.41580] [PMID: 32206116]
[125]
Willms E, Johansson HJ, Mäger I, Lee Y, Blomberg KEM, Sadik M. Cells release subpopulations of exosomes with distinct molecular and biological properties. Sci Rep 2016.
[http://dx.doi.org/10.1038/srep22519]
[126]
Collino F, Pomatto M, Bruno S, et al. Exosome and microvesicle-enriched fractions isolated from mesenchymal stem cells by gradient separation showed different molecular signatures and functions on renal tubular epithelial cells. Stem Cell Rev Rep 2017; 13(2): 226-43.
[http://dx.doi.org/10.1007/s12015-016-9713-1] [PMID: 28070858]
[127]
Wang X, Omar O, Vazirisani F, Thomsen P, Ekströ K. Mesenchymal stem cell-derived exosomes have altered microRNA profiles and induce osteogenic differentiation depending on the stage of differentiation. PloS one 2018; 13(2): e0193059.
[http://dx.doi.org/10.1371/journal.pone.0193059]
[128]
Shelke GV, Lässer C, Gho YS, Lötvall J. Importance of exosome depletion protocols to eliminate functional and RNA-containing extracellular vesicles from fetal bovine serum. J Extracell Vesicles 2014; 3(1): 24783.
[http://dx.doi.org/10.3402/jev.v3.24783] [PMID: 25317276]
[129]
Gardiner C, Vizio DD, Sahoo S, et al. Techniques used for the isolation and characterization of extracellular vesicles: Results of a worldwide survey. J Extracell Vesicles 2016; 5(1): 32945.
[130]
Pirkmajer S, Chibalin AV. Serum starvation: Caveat emptor. Am J Physiol Cell Physiol 2011; 301(2): C272-9.
[http://dx.doi.org/10.1152/ajpcell.00091.2011] [PMID: 21613612]

Rights & Permissions Print Cite
Article Metrics
46
1
© 2024 Bentham Science Publishers | Privacy Policy