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Journal of Neurorestoratology  2019, Vol. 7 Issue (2): 55-62    doi: 10.26599/JNR.2019.9040011
Review Article     
The cell repair research of spinal cord injury: a review of cell transplantation to treat spinal cord injury
Zhenrong Zhang1, Fangyong Wang1,2,(✉), Mingjie Song1
1 School of Rehabilitation, Capital Medical University, Beijing 100068, China
2 Department of Spine and Spinal Cord Surgery, Beijing Bo’ai Hospital, China Rehabilitation Research Center, Beijing 100068, China
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Through retrospective analysis of the literature on the cell repair of spinal cord injury worldwide, it is found that the mechanism of cell transplantation repairing spinal cord injury is mainly to replace damaged neurons, protect host neurons, prevent apoptosis, promote axonal regeneration and synapse formation, promote myelination, and secrete trophic factors or growth factors to improve microenvironment. A variety of cells are used to repair spinal cord injury. Stem cells include multipotent stem cells, embryonic stem cells, and induced pluripotent stem cells. The multipotent stem cells are mainly various types of mesenchymal stem cells and neural stem cells. Non-stem cells include olfactory ensheathing cells and Schwann cells. Transplantation of inhibitory interneurons to alleviate neuropathic pain in patients is receiving widespread attention. Different types of cell transplantation have their own advantages and disadvantages, and multiple cell transplantation may be more helpful to the patient’s functional recovery. These cells have certain effects on the recovery of neurological function and the improvement of complications, but further exploration is needed in clinical application. The application of a variety of cell transplantation, gene technology, bioengineering and other technologies has made the prospect of cell transplantation more extensive. There is a need to find a safe and effective comprehensive treatment to maximize and restore the patient’s performance.

Key wordsspinal cord injury (SCI)      cell transplantation      nerve repair     
Received: 03 June 2019      Published: 22 July 2019
Corresponding Authors: Fangyong Wang   
Cite this article:

Zhenrong Zhang, Fangyong Wang, Mingjie Song. The cell repair research of spinal cord injury: a review of cell transplantation to treat spinal cord injury. Journal of Neurorestoratology, 2019, 7: 55-62.

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[1]   Jazayeri SB, Beygi S, Shokraneh F, et al. Incidence of traumatic spinal cord injury worldwide: a systematic review. Eur Spine J. 2015, 24(5): 905-918.
[2]   Kang Y, Ding H, Zhou HX, et al. Epidemiology of worldwide spinal cord injury: a literature review. J Neurorestoratology. 2017, 6: 1-9.
[3]   Yang R, Guo L, Wang P, et al. Epidemiology of spinal cord injuries and risk factors for complete injuries in Guangdong, China: a retrospective study. PLoS One. 2014, 9(1): e84733.
[4]   Burt AA. (iii) The epidemiology, natural history and prognosis of spinal cord injury. Curr Orthop. 2004, 18(1): 26-32.
[5]   Kumar R, Lim J, Mekary RA, et al. Traumatic spinal injury: global epidemiology and worldwide volume. World Neurosurg. 2018, 113: e345-e363.
[6]   Ackery A, Tator C, Krassioukov A. A global perspective on spinal cord injury epidemiology. J Neurotrauma. 2004, 21(10): 1355-1370.
[7]   Tator CH, Fehlings MG. Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg. 1991, 75(1): 15-26.
[8]   Shende P, Subedi M. Pathophysiology, mechanisms and applications of mesenchymal stem cells for the treatment of spinal cord injury. Biomed Pharmacother. 2017, 91: 693-706.
[9]   Forostyak S, Jendelova P, Sykova E. The role of mesenchymal stromal cells in spinal cord injury, regenerative medicine and possible clinical applications. Biochimie. 2013, 95(12): 2257-2270.
[10]   Kim YH, Ha KY, Kim SI. Spinal cord injury and related clinical trials. Clin Orthop Surg. 2017, 9(1): 1.
[11]   Oliveri RS, Bello S, Biering-S?rensen F. Mesenchymal stem cells improve locomotor recovery in traumatic spinal cord injury: systematic review with meta-analyses of rat models. Neurobiol Dis. 2014, 62: 338-353.
[12]   Llewellyn-Smith IJ, Basbaum AI, Bráz JM. Long-term, dynamic synaptic reorganization after GABAergic precursor cell transplantation into adult mouse spinal cord. J Comp Neurol. 2018, 526(3): 480-495.
[13]   Lu P, Woodruff G, Wang YZ, et al. Long-distance axonal growth from human induced pluripotent stem cells after spinal cord injury. Neuron. 2014, 83(4): 789-796.
[14]   Lin XY, Lai BQ, Zeng X, et al. Cell transplantation and neuroengineering approach for spinal cord injury treatment: A summary of current laboratory findings and review of literature. Cell Transplant. 2016, 25(8): 1425-1438.
[15]   Iyer NR, Wilems TS, Sakiyama-Elbert SE. Stem cells for spinal cord injury: Strategies to inform differentiation and transplantation. Biotechnol Bioeng. 2017, 114(2): 245-259.
[16]   Wu GH, Shi HJ, Che MT, et al. Recovery of paralyzed limb motor function in canine with complete spinal cord injury following implantation of MSC-derived neural network tissue. Biomaterials. 2018, 181: 15-34.
[17]   Zhou ZL, Zhang H, Jin AM, et al. A combination of taxol infusion and human umbilical cord mesenchymal stem cells transplantation for the treatment of rat spinal cord injury. Brain Res. 2012, 1481: 79-89.
[18]   Shahrezaie M, Mansour RN, Nazari B, et al. Improved stem cell therapy of spinal cord injury using GDNF-overexpressed bone marrow stem cells in a rat model. Biologicals. 2017, 50: 73-80.
[19]   Nejati-Koshki K, Mortazavi Y, Pilehvar-Soltanahmadi Y, et al. An update on application of nanotechnology and stem cells in spinal cord injury regeneration. Biomed Pharmacother. 2017, 90: 85-92.
[20]   Jung DI, Ha J, Kang BT, et al. A comparison of autologous and allogenic bone marrow-derived mesenchymal stem cell transplantation in canine spinal cord injury. J Neurol Sci. 2009, 285(1/2): 67-77.
[21]   Ballen KK, Gluckman E, Broxmeyer HE. Umbilical cord blood transplantation: the first 25 years and beyond. Blood. 2013, 122(4): 491-498.
[22]   Bai LP, Li DT, Li J, et al. Bioactive molecules derived from umbilical cord mesenchymal stem cells. Acta Histochem. 2016, 118(8): 761-769.
[23]   Kern S, Eichler H, Stoeve J, et al. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006, 24(5): 1294-1301.
[24]   Borghesi J, Ferreira Lima M, Mario LC, et al. Canine amniotic membrane mesenchymal stromal/stem cells: Isolation, characterization and differentiation. Tissue Cell. 2019, 58: 99-106.
[25]   Ohta Y, Hamaguchi A, Ootaki M, et al. Intravenous infusion of adipose-derived stem/stromal cells improves functional recovery of rats with spinal cord injury. Cytotherapy. 2017, 19(7): 839-848.
[26]   Hur JW, Cho TH, Park DH, et al. Intrathecal transplantation of autologous adipose-derived mesenchymal stem cells for treating spinal cord injury: A human trial. J Spinal Cord Med. 2016, 39(6): 655-664.
[27]   Wu B, Sun L, Li PJ, et al. Transplantation of oligodendrocyte precursor cells improves myelination and promotes functional recovery after spinal cord injury. Injury. 2012, 43(6): 794-801.
[28]   Li N, Leung GK. Oligodendrocyte precursor cells in spinal cord injury: A review and update. Biomed Res Int. 2015, 2015: 235195.
[29]   Priest CA, Manley NC, Denham J, et al. Preclinical safety of human embryonic stem cell-derived oligodendrocyte progenitors supporting clinical trials in spinal cord injury. Regen Med. 2015, 10(8): 939-958.
[30]   Kumamaru H, Saiwai H, Kubota K, et al. Therapeutic activities of engrafted neural stem/precursor cells are not dormant in the chronically injured spinal cord. Stem Cells. 2013, 31(8): 1535-1547.
[31]   Cheng I, Githens M, Smith RL, et al. Local versus distal transplantation of human neural stem cells following chronic spinal cord injury. Spine J. 2016, 16(6): 764-769.
[32]   Curtis E, Martin JR, Gabel B, et al. A first-in-human, phase I study of neural stem cell transplantation for chronic spinal cord injury. Cell Stem Cell. 2018, 22(6): 941-950.e6.
[33]   Ilic D, Devito L, Miere C, et al. Human embryonic and induced pluripotent stem cells in clinical trials. Br Med Bull. 2015, 116: 19-27.
[34]   Vismara I, Papa S, Rossi F, et al. Current options for cell therapy in spinal cord injury. Trends Mol Med. 2017, 23(9): 831-849.
[35]   Goul?o M, Lepore AC. IPS cell transplantation for traumatic spinal cord injury. CSCR. 2016, 11(4): 321-328.
[36]   Young W. Spinal cord regeneration. Cell Transplant. 2014, 23(4/5): 573-611.
[37]   Qin C, Guo Y, Yang DG, et al. Induced pluripotent stem cell transplantation improves locomotor recovery in rat models of spinal cord injury: a systematic review and meta-analysis of randomized controlled trials. Cell Physiol Biochem. 2018, 47(5): 1835-1852.
[38]   Doulames VM, Plant GW. Induced pluripotent stem cell therapies for cervical spinal cord injury. Int J Mol Sci. 2016, 17(4): 530.
[39]   Zhong WT, Bian KP, Hu YN, et al. Lysophosphatidic acid guides the homing of transplanted olfactory ensheathing cells to the lesion site after spinal cord injury in rats. Exp Cell Res. 2019, 379(1): 65-72.
[40]   Chen L, Zhang Y, He X, et al. Comparison of intramedullary transplantation of olfactory ensheathing cell for patients with chronic complete spinal cord injury worldwide. J Neurorestoratology. 2018, 1(6):146-151.
[41]   Zheng ZC, Du XJ, Zhang KG, et al. Olfactory ensheathing cell transplantation inhibits P2X4 receptor overexpression in spinal cord injury rats with neuropathic pain. Neurosci Lett. 2017, 651: 171-176.
[42]   Hosseini M, Yousefifard M, Baikpour M, et al. The efficacy of Schwann cell transplantation on motor function recovery after spinal cord injuries in animal models: A systematic review and meta-analysis. J Chem Neuroanat. 2016, 78: 102-111.
[43]   Anderson KD, Guest JD, Dietrich WD, et al. Safety of autologous human schwann cell transplantation in subacute thoracic spinal cord injury. J Neurotrauma. 2017, 34(21): 2950-2963.
[44]   Chen XM, Xue BH, Li YP, et al. Meta-analysis of stem cell transplantation for reflex hypersensitivity after spinal cord injury. Neuroscience. 2017, 363: 66-75.
[45]   Fandel TM, Trivedi A, Nicholas CR, et al. Transplanted human stem cell-derived interneuron precursors mitigate mouse bladder dysfunction and central neuropathic pain after spinal cord injury. Cell Stem Cell. 2016, 19(4): 544-557.
[46]   Blesch A. Human ESC-derived interneurons improve major consequences of spinal cord injury. Cell Stem Cell. 2016, 19(4): 423-424.
[47]   Marín O. Cellular and molecular mechanisms controlling the migration of neocortical interneurons. Eur J Neurosci. 2013, 38(1): 2019-2029.
[48]   Etlin A, Bráz JM, Kuhn JA, et al. Functional synaptic integration of forebrain GABAergic precursors into the adult spinal cord. J Neurosci. 2016, 36(46): 11634-11645.
[49]   Bráz JM, Sharif-Naeini R, Vogt D, et al. Forebrain GABAergic neuron precursors integrate into adult spinal cord and reduce injury-induced neuropathic pain. Neuron. 2012, 74(4): 663-675.
[50]   Wei GJ, An G, Shi ZW, et al. Suppression of MicroRNA-383 enhances therapeutic potential of human bone-marrow- derived mesenchymal stem cells in treating spinal cord injury via GDNF. Cell Physiol Biochem. 2017, 41(4): 1435-1444.
[51]   Stewart AN, Kendziorski G, Deak ZM, et al. Transplantation of mesenchymal stem cells that overexpress NT-3 produce motor improvements without axonal regeneration following complete spinal cord transections in rats. Brain Res. 2018, 1699: 19-33.
[52]   Shang AJ, Hong SQ, Xu Q, et al. NT-3-secreting human umbilical cord mesenchymal stromal cell transplantation for the treatment of acute spinal cord injury in rats. Brain Res. 2011, 1391: 102-113.
[53]   Ye Y, Feng TT, Peng YR, et al. The treatment of spinal cord injury in rats using bone marrow-derived neural-like cells induced by cerebrospinal fluid. Neurosci Lett. 2018, 666: 85-91.
[54]   Galhom RA, Hussein Abd El Raouf HH, Mohammed Ali MH. Role of bone marrow derived mesenchymal stromal cells and Schwann-like cells transplantation on spinal cord injury in adult male albino rats. Biomed Pharmacother. 2018, 108: 1365-1375.
[55]   Hacein-Bey-Abina S, Von Kalle C, Schmidt M, et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science. 2003, 302(5644): 415-419.
[56]   Muheremu A, Peng J, Ao Q. Stem cell based therapies for spinal cord injury. Tissue Cell. 2016, 48(4): 328-333.
[57]   Agbay A, Edgar JM, Robinson M, et al. Biomaterial strategies for delivering stem cells as a treatment for spinal cord injury. Cells Tissues Organs (Print). 2016, 202(1/2): 42-51.
[58]   Li XR, Fan CX, Xiao ZF, et al. A collagen microchannel scaffold carrying paclitaxel-liposomes induces neuronal differentiation of neural stem cells through Wnt/β-catenin signaling for spinal cord injury repair. Biomaterials. 2018, 183: 114-127.
[59]   Koffler J, Zhu W, Qu X, et al. Biomimetic 3D-printed scaffolds for spinal cord injury repair. Nat Med. 2019, 25(2): 263-269.
[60]   Xie XM, Shi LL, Shen L, et al. Co-transplantation of MRF- overexpressing oligodendrocyte precursor cells and Schwann cells promotes recovery in rat after spinal cord injury. Neurobiol Dis. 2016, 94: 196-204.
[61]   Elboghdady I, Hassanzadeh H, Stein BE, et al. Controversies and potential risk of mesenchymal stem cells application. Semin Spine Surg. 2015, 27(2): 103-106.
[62]   Huang HY, Sharma HS, Chen L, et al. 2018 Yearbook of Neurorestoratology. J Neurorestroratology. 2019, 1(7): 8-17.
[63]   Huang HY, Shanker S H, Lin C, et al. Review of clinical neurorestorative strategies for spinal cord injury: exploring history and latest progresses. J Neurorestroratology. 2018, 1(6): 171-178.
[64]   Baastrup C, Maersk-Moller CC, Nyengaard JR, et al. Spinal-, brainstem- and cerebrally mediated responses at- and below- level of a spinal cord contusion in rats: evaluation of pain-Like behavior. Pain. 2010, 151(3): 670-679.
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