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Current Stem Cell Research & Therapy

Editor-in-Chief

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

Review Article

Transplantation Strategies for Spinal Cord Injury Based on Microenvironment Modulation

Author(s): Jiawei Shu, Feng Cheng, Zhe Gong, Liwei Ying, Chenggui Wang, Chao Yu, Xiaopeng Zhou, Mu Xiao, Jingkai Wang, Kaishun Xia, Xianpeng Huang, Yiqing Tao, Kesi Shi, Yuemei Liu, Chengzhen Liang, Qixin Chen*, Xinhua Feng* and Fangcai Li*

Volume 15, Issue 6, 2020

Page: [522 - 530] Pages: 9

DOI: 10.2174/1574888X15666200421112622

Price: $65

Abstract

Spinal cord injury (SCI) is different from peripheral nerve injury; it results in devastating and permanent damage to the spine, leading to severe motor, sensory and autonomic dysfunction. SCI produces a complex microenvironment that can result in hemorrhage, inflammation and scar formation. Not only does it significantly limit regeneration, but it also challenges a multitude of transplantation strategies. In order to promote regeneration, researchers have recently begun to focus their attention on strategies that manipulate the complicated microenvironment produced by SCI. And some have achieved great therapeutic effects. Hence, reconstructing an appropriate microenvironment after transplantation could be a potential therapeutic solution for SCI. In this review, first, we aim to summarize the influential compositions of the microenvironment and their different effects on regeneration. Second, we highlight recent research that used various transplantation strategies to modulate different microenvironments produced by SCI in order to improve regeneration. Finally, we discuss future transplantation strategies regarding SCI.

Keywords: Spinal cord injury, microenvironment, regeneration, transplantation, stem cells, biomaterials.

[1]
Lee BB, Cripps RA, Fitzharris M, Wing PC. The global map for traumatic spinal cord injury epidemiology: update 2011, global incidence rate. Spinal Cord 2014; 52(2): 110-6.
[http://dx.doi.org/10.1038/sc.2012.158] [PMID: 23439068]
[2]
Wu Q, Li YL, Ning GZ, et al. Epidemiology of traumatic cervical spinal cord injury in Tianjin, China. Spinal Cord 2012; 50(10): 740-4.
[http://dx.doi.org/10.1038/sc.2012.42] [PMID: 22525311]
[3]
Bartanusz V, Jezova D, Alajajian B, Digicaylioglu M. The blood-spinal cord barrier: morphology and clinical implications. Ann Neurol 2011; 70(2): 194-206.
[http://dx.doi.org/10.1002/ana.22421] [PMID: 21674586]
[4]
Vismara I, Papa S, Rossi F, Forloni G, Veglianese P. Current Options for Cell Therapy in Spinal Cord Injury. Trends Mol Med 2017; 23(9): 831-49.
[http://dx.doi.org/10.1016/j.molmed.2017.07.005] [PMID: 28811172]
[5]
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]
[6]
Chhabra HS, Sarda K. Clinical translation of stem cell based interventions for spinal cord injury - Are we there yet? Adv Drug Deliv Rev 2017; 120: 41-9.
[http://dx.doi.org/10.1016/j.addr.2017.09.021] [PMID: 28964881]
[7]
Barnabé-Heider F, Frisén J. Stem cells for spinal cord repair. Cell Stem Cell 2008; 3(1): 16-24.
[http://dx.doi.org/10.1016/j.stem.2008.06.011] [PMID: 18593555]
[8]
Okano H, Yamanaka S. iPS cell technologies: significance and applications to CNS regeneration and disease. Mol Brain 2014; 7: 22.
[http://dx.doi.org/10.1186/1756-6606-7-22] [PMID: 24685317]
[9]
Courtine G, Sofroniew MV. Spinal cord repair: advances in biology and technology. Nat Med 2019; 25(6): 898-908.
[http://dx.doi.org/10.1038/s41591-019-0475-6] [PMID: 31160817]
[10]
Ramer LM, Ramer MS, Bradbury EJ. Restoring function after spinal cord injury: towards clinical translation of experimental strategies. Lancet Neurol 2014; 13(12): 1241-56.
[http://dx.doi.org/10.1016/S1474-4422(14)70144-9] [PMID: 25453463]
[11]
Fan B, Wei Z, Yao X, et al. Microenvironment imbalance of spinal cord injury. Cell Transplant 2018; 27(6): 853-66.
[http://dx.doi.org/10.1177/0963689718755778] [PMID: 29871522]
[12]
Curtis E, Martin JR, Gabel B, et al. A First-in-Human, Phase I Study of Neural Stem Cell Transplan-tation for Chronic Spinal Cord Injury Cell Stem Cell 2018; 22(6): 941-50..
[13]
Cyranoski D. Japan’s approval of stem-cell treatment for spinal-cord injury concerns scientists. Nature 2019; 565(7741): 544-5.
[http://dx.doi.org/10.1038/d41586-019-00178-x] [PMID: 30696963]
[14]
Assinck P, Duncan GJ, Hilton BJ, Plemel JR, Tetzlaff W. Cell transplantation therapy for spinal cord injury. Nat Neurosci 2017; 20(5): 637-47.
[http://dx.doi.org/10.1038/nn.4541] [PMID: 28440805]
[15]
Deng W, Shao F, He Q, et al. EMSCs Build an All-in-One Niche via Cell-Cell Lipid Raft Assembly for Promoted Neuronal but Suppressed Astroglial Differentiation of Neural Stem Cells. Adv Mater 2019; 31(10)e1806861
[http://dx.doi.org/10.1002/adma.201806861] [PMID: 30633831]
[16]
Ahuja CS, Nori S, Tetreault L, et al. Traumatic Spinal Cord Injury-Repair and Regeneration. Neurosurgery 2017; 80(3S): S9-S22.
[http://dx.doi.org/10.1093/neuros/nyw080] [PMID: 28350947]
[17]
McKinley WO, Seel RT, Hardman JT. Nontraumatic spinal cord injury: incidence, epidemiology, and functional outcome. Arch Phys Med Rehabil 1999; 80(6): 619-23.
[http://dx.doi.org/10.1016/S0003-9993(99)90162-4] [PMID: 10378485]
[18]
Kwon BK, Tetzlaff W, Grauer JN, Beiner J, Vaccaro AR. Pathophysiology and pharmacologic treatment of acute spinal cord injury. Spine J 2004; 4(4): 451-64.
[http://dx.doi.org/10.1016/j.spinee.2003.07.007] [PMID: 15246307]
[19]
Norenberg MD, Smith J, Marcillo A. The pathology of human spinal cord injury: defining the problems. J Neurotrauma 2004; 21(4): 429-40.
[http://dx.doi.org/10.1089/089771504323004575] [PMID: 15115592]
[20]
Oyinbo CA. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp (Warsz) 2011; 71(2): 281-99.
[PMID: 21731081]
[21]
Nishimura S, Yasuda A, Iwai H, et al. Time-dependent changes in the microenvironment of injured spinal cord affects the therapeutic potential of neural stem cell transplantation for spinal cord injury. Mol Brain 2013; 6: 3.
[http://dx.doi.org/10.1186/1756-6606-6-3] [PMID: 23298657]
[22]
Benton RL, Hagg T. Vascular Pathology as a Potential Therapeutic Target in SCI. Transl Stroke Res 2011; 2(4): 556-74.
[http://dx.doi.org/10.1007/s12975-011-0128-7] [PMID: 24323683]
[23]
Hao J, Li B, Duan HQ, et al. Mechanisms underlying the promotion of functional recovery by deferoxamine after spinal cord injury in rats. Neural Regen Res 2017; 12(6): 959-68.
[http://dx.doi.org/10.4103/1673-5374.208591] [PMID: 28761430]
[24]
Okon EB, Streijger F, Lee JHT, Anderson LM, Russell AK, Kwon BK. Intraparenchymal microdialysis after acute spinal cord injury reveals differential metabolic responses to contusive versus compressive mechanisms of injury. J Neurotrauma 2013; 30(18): 1564-76.
[http://dx.doi.org/10.1089/neu.2013.2956] [PMID: 23768189]
[25]
Grégoire CA, Goldenstein BL, Floriddia EM, Barnabé-Heider F, Fernandes KJ. Endogenous neural stem cell responses to stroke and spinal cord injury. Glia 2015; 63(8): 1469-82.
[http://dx.doi.org/10.1002/glia.22851] [PMID: 25921491]
[26]
Plemel JR, Keough MB, Duncan GJ, et al. Remyelination after spinal cord injury: is it a target for repair? Prog Neurobiol 2014; 117: 54-72.
[http://dx.doi.org/10.1016/j.pneurobio.2014.02.006] [PMID: 24582777]
[27]
David S, Kroner A. Repertoire of microglial and macrophage responses after spinal cord injury. Nat Rev Neurosci 2011; 12(7): 388-99.
[http://dx.doi.org/10.1038/nrn3053] [PMID: 21673720]
[28]
Ren Y, Young W. Managing inflammation after spinal cord injury through manipulation of macrophage function. Neural Plast 2013. 2013945034
[http://dx.doi.org/10.1155/2013/945034] [PMID: 24288627]
[29]
Rolls A, Shechter R, Schwartz M. The bright side of the glial scar in CNS repair. Nat Rev Neurosci 2009; 10(3): 235-41.
[http://dx.doi.org/10.1038/nrn2591] [PMID: 19229242]
[30]
Mekhail M, Almazan G, Tabrizian M. Oligodendrocyte-protection and remyelination post-spinal cord injuries: a review. Prog Neurobiol 2012; 96(3): 322-39.
[http://dx.doi.org/10.1016/j.pneurobio.2012.01.008] [PMID: 22307058]
[31]
Lane SW, Williams DA, Watt FM. Modulating the stem cell niche for tissue regeneration. Nat Biotechnol 2014; 32(8): 795-803.
[http://dx.doi.org/10.1038/nbt.2978] [PMID: 25093887]
[32]
Gadani SP, Walsh JT, Lukens JR, Kipnis J. Dealing with Danger in the CNS: The Response of the Immune System to Injury. Neuron 2015; 87(1): 47-62.
[http://dx.doi.org/10.1016/j.neuron.2015.05.019] [PMID: 26139369]
[33]
Jin X, Yamashita T. Microglia in central nervous system repair after injury. J Biochem 2016; 159(5): 491-6.
[http://dx.doi.org/10.1093/jb/mvw009] [PMID: 26861995]
[34]
Liu NK, Xu XM. Neuroprotection and its molecular mechanism following spinal cord injury. Neural Regen Res 2012; 7(26): 2051-62.
[PMID: 25624837]
[35]
David S, Greenhalgh AD, Kroner A. Macrophage and microglial plasticity in the injured spinal cord. Neuroscience 2015; 307: 311-8.
[http://dx.doi.org/10.1016/j.neuroscience.2015.08.064] [PMID: 26342747]
[36]
Kong X, Gao J. Macrophage polarization: a key event in the secondary phase of acute spinal cord injury. J Cell Mol Med 2017; 21(5): 941-54.
[http://dx.doi.org/10.1111/jcmm.13034] [PMID: 27957787]
[37]
Tran AP, Warren PM, Silver J. The Biology of Regeneration Failure and Success After Spinal Cord Injury. Physiol Rev 2018; 98(2): 881-917.
[http://dx.doi.org/10.1152/physrev.00017.2017] [PMID: 29513146]
[38]
Dias DO, Kim H, Holl D, et al. Reducing Pericyte-Derived Scarring Promotes Recovery after Spinal Cord Injury. Cell 2018; 173(1): 153-165.e22.
[http://dx.doi.org/10.1016/j.cell.2018.02.004] [PMID: 29502968]
[39]
Hara M, Kobayakawa K, Ohkawa Y, et al. Interaction of reactive astrocytes with type I collagen induces astrocytic scar formation through the integrin-N-cadherin pathway after spinal cord injury. Nat Med 2017; 23(7): 818-28.
[http://dx.doi.org/10.1038/nm.4354] [PMID: 28628111]
[40]
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]
[41]
Horner PJ, Reier PJ, Stokes BT. Quantitative analysis of vascularization and cytochrome oxidase following fetal transplantation in the contused rat spinal cord. J Comp Neurol 1996; 364(4): 690-703.
[http://dx.doi.org/10.1002/(SICI)1096-9861(19960122)364:4<690:AID-CNE7>3.0.CO;2-Z] [PMID: 8821455]
[42]
López-Vales R, García-Alías G, Forés J, Navarro X, Verdú E. Increased expression of cyclo-oxygenase 2 and vascular endothelial growth factor in lesioned spinal cord by transplanted olfactory ensheathing cells. J Neurotrauma 2004; 21(8): 1031-43.
[http://dx.doi.org/10.1089/0897715041651105] [PMID: 15319002]
[43]
Lee KH, Pyeon HJ, Nam H, et al. Significant therapeutic effects of adult human multipotent neural cells on spinal cord injury. Stem Cell Res (Amst) 2018; 31: 71-8.
[http://dx.doi.org/10.1016/j.scr.2018.07.006] [PMID: 30031233]
[44]
López-Dolado E, González-Mayorga A, Gutiérrez MC, Serrano MC. Immunomodulatory and angiogenic responses induced by graphene oxide scaffolds in chronic spinal hemisected rats. Biomaterials 2016; 99: 72-81.
[http://dx.doi.org/10.1016/j.biomaterials.2016.05.012] [PMID: 27214651]
[45]
Hejčl A, Růžička J, Kekulová K, et al. Modified Methacrylate Hydrogels Improve Tissue Repair after Spinal Cord Injury. Int J Mol Sci 2018; 19(9)E2481
[http://dx.doi.org/10.3390/ijms19092481] [PMID: 30131482]
[46]
Li Y, Lucas-Osma AM, Black S, et al. Pericytes impair capillary blood flow and motor function after chronic spinal cord injury. Nat Med 2017; 23(6): 733-41.
[http://dx.doi.org/10.1038/nm.4331] [PMID: 28459438]
[47]
Almeida VM, Paiva AE, Sena IFG, Mintz A, Magno LAV, Birbrair A. Pericytes Make Spinal Cord Breathless after Injury. Neuroscientist 2018; 24(5): 440-7.
[http://dx.doi.org/10.1177/1073858417731522] [PMID: 29283016]
[48]
Li X, Zhao Y, Cheng S, et al. Cetuximab modified collagen scaffold directs neurogenesis of injury-activated endogenous neural stem cells for acute spinal cord injury repair. Biomaterials 2017; 137: 73-86.
[http://dx.doi.org/10.1016/j.biomaterials.2017.05.027] [PMID: 28544974]
[49]
Yang Z, Zhang A, Duan H, et al. NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury. Proc Natl Acad Sci USA 2015; 112(43): 13354-9.
[http://dx.doi.org/10.1073/pnas.1510194112] [PMID: 26460015]
[50]
Koffler J, Zhu W, Qu X, et al. Biomimetic 3D-printed scaffolds for spinal cord injury repair. Nat Med 2019; 25(2): 263-9.
[http://dx.doi.org/10.1038/s41591-018-0296-z] [PMID: 30643285]
[51]
Hernández J, Torres-Espín A, Navarro X. Adult stem cell transplants for spinal cord injury repair: current state in preclinical research. Curr Stem Cell Res Ther 2011; 6(3): 273-87.
[http://dx.doi.org/10.2174/157488811796575323] [PMID: 21476980]
[52]
Ra JC, Shin IS, Kim SH, et al. Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. Stem Cells Dev 2011; 20(8): 1297-308.
[http://dx.doi.org/10.1089/scd.2010.0466] [PMID: 21303266]
[53]
Cheng H, Liu X, Hua R, et al. Clinical observation of umbilical cord mesenchymal stem cell transplantation in treatment for sequelae of thoracolumbar spinal cord injury. J Transl Med 2014; 12: 253.
[http://dx.doi.org/10.1186/s12967-014-0253-7] [PMID: 25209445]
[54]
El-Kheir WA, Gabr H, Awad MR, et al. Autologous bone marrow-derived cell therapy combined with physical therapy induces functional improvement in chronic spinal cord injury patients. Cell Transplant 2014; 23(6): 729-45.
[http://dx.doi.org/10.3727/096368913X664540] [PMID: 23452836]
[55]
Silvestro S, Bramanti P, Trubiani O, Mazzon E. Stem Cells Therapy for Spinal Cord Injury: An Overview of Clinical Trials. Int J Mol Sci 2020; 21(2)E659
[http://dx.doi.org/10.3390/ijms21020659] [PMID: 31963888]
[56]
Liu J, Han D, Wang Z, et al. Clinical analysis of the treatment of spinal cord injury with umbilical cord mesenchymal stem cells. Cytotherapy 2013; 15(2): 185-91.
[http://dx.doi.org/10.1016/j.jcyt.2012.09.005] [PMID: 23321330]
[57]
Åkesson E, Sundström E. Human neural progenitor cells in central nervous system lesions. Best Pract Res Clin Obstet Gynaecol 2016; 31: 69-81.
[http://dx.doi.org/10.1016/j.bpobgyn.2015.11.020] [PMID: 26803559]
[58]
Tsuji O, Sugai K, Yamaguchi R, et al. Concise Review: Laying the Groundwork for a First-In-Human Study of an Induced Pluripotent Stem Cell-Based Intervention for Spinal Cord Injury. Stem Cells 2019; 37(1): 6-13.
[http://dx.doi.org/10.1002/stem.2926] [PMID: 30371964]
[59]
Riemann L, Younsi A, Scherer M, et al. Transplantation of Neural Precursor Cells Attenuates Chronic Immune Environment in Cervical Spinal Cord Injury. Front Neurol 2018; 9: 428.
[http://dx.doi.org/10.3389/fneur.2018.00428] [PMID: 29951030]
[60]
Zhang J, Chen H, Duan Z, et al. The Effects of Co-transplantation of Olfactory Ensheathing Cells and Schwann Cells on Local Inflammation Environment in the Contused Spinal Cord of Rats. Mol Neurobiol 2017; 54(2): 943-53.
[http://dx.doi.org/10.1007/s12035-016-9709-5] [PMID: 26790672]
[61]
Iwasaki M, Wilcox JT, Nishimura Y, et al. Synergistic effects of self-assembling peptide and neural stem/progenitor cells to promote tissue repair and forelimb functional recovery in cervical spinal cord injury. Biomaterials 2014; 35(9): 2617-29.
[http://dx.doi.org/10.1016/j.biomaterials.2013.12.019] [PMID: 24406216]
[62]
Li G, Che MT, Zhang K, et al. Graft of the NT-3 persistent delivery gelatin sponge scaffold promotes axon regeneration, attenuates inflammation, and induces cell migration in rat and canine with spinal cord injury. Biomaterials 2016; 83: 233-48.
[http://dx.doi.org/10.1016/j.biomaterials.2015.11.059] [PMID: 26774562]
[63]
Sun G, Yang S, Cai H, et al. Molybdenum disulfide nanoflowers mediated anti-inflammation macrophage modulation for spinal cord injury treatment. J Colloid Interface Sci 2019; 549: 50-62.
[http://dx.doi.org/10.1016/j.jcis.2019.04.047] [PMID: 31015056]
[64]
Fan L, Liu C, Chen X, et al. Directing Induced Pluripotent Stem Cell Derived Neural Stem Cell Fate with a Three-Dimensional Biomimetic Hydrogel for Spinal Cord Injury Repair. ACS Appl Mater Interfaces 2018; 10(21): 17742-55.
[http://dx.doi.org/10.1021/acsami.8b05293] [PMID: 29733569]
[65]
Wang XJ, Peng CH, Zhang S, et al. Polysialic-Acid-Based Micelles Promote Neural Regeneration in Spinal Cord Injury Therapy. Nano Lett 2019; 19(2): 829-38.
[http://dx.doi.org/10.1021/acs.nanolett.8b04020] [PMID: 30605619]
[66]
Thompson RE, Pardieck J, Smith L, et al. Effect of hyaluronic acid hydrogels containing astrocyte-derived extracellular matrix and/or V2a interneurons on histologic outcomes following spinal cord injury. Biomaterials 2018; 162: 208-23.
[http://dx.doi.org/10.1016/j.biomaterials.2018.02.013] [PMID: 29459311]
[67]
Führmann T, Anandakumaran PN, Shoichet MS. Combinatorial Therapies After Spinal Cord Injury: How Can Biomaterials Help? Adv Healthc Mater 2017; 6(10)
[http://dx.doi.org/10.1002/adhm.201601130] [PMID: 28247563]
[68]
Liu S, Xie YY, Wang B. Role and prospects of regenerative biomaterials in the repair of spinal cord injury. Neural Regen Res 2019; 14(8): 1352-63.
[http://dx.doi.org/10.4103/1673-5374.253512] [PMID: 30964053]
[69]
Nori S, Nakamura M, Okano H. Plasticity and regeneration in the injured spinal cord after cell transplantation therapy Prog Brain Res 2017; 231: 33-56.
[http://dx.doi.org/10.1016/bs.pbr.2016.12.007] [PMID: 28554400]

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