Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

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

Review Article

hiPSC-Neural Stem/Progenitor Cell Transplantation Therapy for Spinal Cord Injury

Author(s): Xiaofeng Du, Asiamah Ernest Amponsah, Desheng Kong, Jingjing He, Zhenhuan Ma, Jun Ma* and Huixian Cui*

Volume 18, Issue 4, 2023

Published on: 16 September, 2022

Page: [487 - 498] Pages: 12

DOI: 10.2174/1574888X17666220509222520

Price: $65

conference banner
Abstract

Spinal cord injury (SCI) is a catastrophic event that incurs substantial personal and social costs. The complex pathophysiology associated with SCI often limits the regeneration of nerve tissue at the injured site and leads to permanent nerve damage. With advances in stem cell biology, the field of regenerative medicine offers the hope of solving this challenging problem. Neural stem/progenitor cells (NSPCs) possess nerve regenerative and neuroprotective effects, and transplanting NSPCs in their optimized form into an injured area holds promising therapeutic potential for SCI. In this review, we summarize the advantages and disadvantages of NSPCs derived from different sources while highlighting the utility of NSPCs derived from induced pluripotent stem cells, an NSPC source with superior advantages, according to data from in vivo animal models and the latest clinical trials.

Keywords: Spinal cord injury, hiPSC, neural stem cell, neural progenitor cell, transplantation, neuroprotective effects.

Graphical Abstract

[1]
National Spinal Cord Injury Statistical Center Spinal Cord Facts and Figures 2021. Available from: https://www.nscisc.uab.edu/ Accessed on July 23, 2021
[2]
Bhatnagar T, Liu J, Yung A, et al. Relating histopathology and mechanical strain in experimental contusion spinal cord injury in a rat model. J Neurotrauma 2016; 33(18): 1685-95.
[http://dx.doi.org/10.1089/neu.2015.4200] [PMID: 26729511]
[3]
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]
[4]
Bethel M, Weaver FM, Bailey L, et al. Risk factors for osteoporotic fractures in persons with spinal cord injuries and disorders. Osteoporos Int 2016; 27(10): 3011-21.
[http://dx.doi.org/10.1007/s00198-016-3627-2] [PMID: 27230522]
[5]
Nakashima H, Tetreault LA, Nagoshi N, et al. Does age affect surgical outcomes in patients with degenerative cervical myelopathy? Results from the prospective multicenter AOSpine International study on 479 patients. J Neurol Neurosurg Psychiatry 2016; 87(7): 734-40.
[http://dx.doi.org/10.1136/jnnp-2015-311074] [PMID: 26420885]
[6]
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]
[7]
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): 7533.
[http://dx.doi.org/10.3390/ijms21207533] [PMID: 33066029]
[8]
Katoh H, Yokota K, Fehlings MG. Regeneration of spinal cord connectivity through stem cell transplantation and biomaterial scaffolds. Front Cell Neurosci 2019; 13: 248.
[http://dx.doi.org/10.3389/fncel.2019.00248] [PMID: 31244609]
[9]
Beattie MS. Inflammation and apoptosis: Linked therapeutic targets in spinal cord injury. Trends Mol Med 2004; 10(12): 580-3.
[http://dx.doi.org/10.1016/j.molmed.2004.10.006] [PMID: 15567326]
[10]
Hilton BJ, Moulson AJ, Tetzlaff W. Neuroprotection and secondary damage following spinal cord injury: Concepts and methods. Neurosci Lett 2017; 652: 3-10.
[http://dx.doi.org/10.1016/j.neulet.2016.12.004] [PMID: 27939975]
[11]
Badhiwala JH, Ahuja CS, Fehlings MG. Time is spine: A review of translational advances in spinal cord injury. J Neurosurg Spine 2018; 30(1): 1-18.
[http://dx.doi.org/10.3171/2018.9.SPINE18682] [PMID: 30611186]
[12]
Pineau I, Lacroix S. Proinflammatory cytokine synthesis in the injured mouse spinal cord: Multiphasic expression pattern and identification of the cell types involved. J Comp Neurol 2007; 500(2): 267-85.
[http://dx.doi.org/10.1002/cne.21149] [PMID: 17111361]
[13]
Hausmann ON. Post-traumatic inflammation following spinal cord injury. Spinal Cord 2003; 41(7): 369-78.
[http://dx.doi.org/10.1038/sj.sc.3101483] [PMID: 12815368]
[14]
Wang Y, Wang H, Tao Y, Zhang S, Wang J, Feng X. Necroptosis inhibitor necrostatin-1 promotes cell protection and physiological function in traumatic spinal cord injury. Neuroscience 2014; 266: 91-101.
[http://dx.doi.org/10.1016/j.neuroscience.2014.02.007] [PMID: 24561219]
[15]
Kwon BK, Grauer JN, Vaccaro AR. The Pathophysiology and pharmacologic treatment of acute spinal cord injury. Spine J 2005; 4(4): 451-64.
[http://dx.doi.org/10.1016/j.spinee.2003.07.007]
[16]
Rowland JW, Hawryluk GW, Kwon B, Fehlings MG. Current status of acute spinal cord injury pathophysiology and emerging therapies: Promise on the horizon. Neurosurg Focus 2008; 25(5): E2.
[http://dx.doi.org/10.3171/FOC.2008.25.11.E2] [PMID: 18980476]
[17]
Ahuja CS, Wilson JR, Nori S, et al. Traumatic spinal cord injury. Nat Rev Dis Primers 2017; 3: 17018.
[http://dx.doi.org/10.1038/nrdp.2017.18] [PMID: 28447605]
[18]
Liddelow SA, Barres BA. Reactive astrocytes: Production, function, and therapeutic potential. Immunity 2017; 46(6): 957-67.
[http://dx.doi.org/10.1016/j.immuni.2017.06.006] [PMID: 28636962]
[19]
Forgione N, Fehlings MG. Rho-ROCK inhibition in the treatment of spinal cord injury. World Neurosurg 2014; 82(3-4): e535-9.
[http://dx.doi.org/10.1016/j.wneu.2013.01.009] [PMID: 23298675]
[20]
Kwon BK, Fisher CG, Dvorak MF, Tetzlaff W. Strategies to promote neural repair and regeneration after spinal cord injury. Spine 2005; 30(17) (Suppl.): S3-S13.
[http://dx.doi.org/10.1097/01.brs.0000175186.17923.87] [PMID: 16138063]
[21]
Chaddah R, Arntfield M, Runciman S, Clarke L, van der Kooy D. Clonal neural stem cells from human embryonic stem cell colonies. J Neurosci 2012; 32(23): 7771-81.
[http://dx.doi.org/10.1523/JNEUROSCI.3286-11.2012] [PMID: 22674254]
[22]
Dessaud E, Ribes V, Balaskas N, et al. Dynamic assignment and maintenance of positional identity in the ventral neural tube by the morphogen sonic hedgehog. PLoS Biol 2010; 8(6), e1000382.
[http://dx.doi.org/10.1371/journal.pbio.1000382] [PMID: 20532235]
[23]
Kulbatski I, Mothe AJ, Keating A, Hakamata Y, Kobayashi E, Tator CH. Oligodendrocytes and radial glia derived from adult rat spinal cord progenitors: Morphological and immunocytochemical characterization. J Histochem Cytochem 2007; 55(3): 209-22.
[http://dx.doi.org/10.1369/jhc.6A7020.2006] [PMID: 17101728]
[24]
Mothe AJ, Zahir T, Santaguida C, Cook D, Tator CH. Neural stem/progenitor cells from the adult human spinal cord are multipotent and self-renewing and differentiate after transplantation. PLoS One 2011; 6(11), e27079.
[http://dx.doi.org/10.1371/journal.pone.0027079] [PMID: 22073257]
[25]
Xu W, Lakshman N, Morshead CM. Building a central nervous system: The neural stem cell lineage revealed. Neurogenesis (Austin) 2017; 4(1), e1300037.
[http://dx.doi.org/10.1080/23262133.2017.1300037] [PMID: 28516107]
[26]
Xu W, Lakshman N, Morshead CM. Stem cells in the adult CNS revealed: Examining their regulation by myelin basic protein. Neural Regen Res 2016; 11(12): 1916-7.
[27]
Dadwal P, Mahmud N, Sinai L, et al. Activating endogenous neural precursor cells using metformin leads to neural repair and functional recovery in a model of childhood brain injury. Stem Cell Reports 2015; 5(2): 166-73.
[http://dx.doi.org/10.1016/j.stemcr.2015.06.011] [PMID: 26235894]
[28]
Goldman S. Stem and progenitor cell-based therapy of the human central nervous system. Nat Biotechnol 2005; 23(7): 862-71.
[http://dx.doi.org/10.1038/nbt1119] [PMID: 16003375]
[29]
Shihabuddin LS, Palmer TD, Gage FH. The search for neural progenitor cells: Prospects for the therapy of neurodegenerative disease. Mol Med Today 1999; 5(11): 474-80.
[http://dx.doi.org/10.1016/S1357-4310(99)01596-8] [PMID: 10529788]
[30]
Clarke DL, Johansson CB, Wilbertz J, et al. Generalized potential of adult neural stem cells. Science 2000; 288(5471): 1660-3.
[http://dx.doi.org/10.1126/science.288.5471.1660] [PMID: 10834848]
[31]
Hefferan MP, Galik J, Kakinohana O, et al. Human neural stem cell replacement therapy for amyotrophic lateral sclerosis by spinal transplantation. PLoS One 2012; 7(8), e42614.
[http://dx.doi.org/10.1371/journal.pone.0042614] [PMID: 22916141]
[32]
Tzeng SF. Neural progenitors isolated from newborn rat spinal cords differentiate into neurons and astroglia. J Biomed Sci 2002; 9(1): 10-6.
[http://dx.doi.org/10.1007/BF02256573] [PMID: 11810020]
[33]
Friedenstein AJ, Chailakhyan RK, Gerasimov UV. Bone marrow osteogenic stem cells: In vitro cultivation and transplantation in diffusion chambers. Cell Tissue Kinet 1987; 20(3): 263-72.
[http://dx.doi.org/10.1111/j.1365-2184.1987.tb01309.x] [PMID: 3690622]
[34]
Kopen GC, Prockop DJ, Phinney DG. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci USA 1999; 96(19): 10711-6.
[http://dx.doi.org/10.1073/pnas.96.19.10711] [PMID: 10485891]
[35]
Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 2000; 61(4): 364-70.
[http://dx.doi.org/10.1002/1097-4547(20000815)61:4<364:AID-JNR2>3.0.CO;2-C] [PMID: 10931522]
[36]
Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature 1981; 292(5819): 154-6.
[http://dx.doi.org/10.1038/292154a0] [PMID: 7242681]
[37]
Sánchez-Martín FJ, Fan Y, Lindquist DM, Xia Y, Puga A. Lead induces similar gene expression changes in brains of gestationally exposed adult mice and in neurons differentiated from mouse embryonic stem cells. PLoS One 2013; 8(11), e80558.
[http://dx.doi.org/10.1371/journal.pone.0080558] [PMID: 24260418]
[38]
Azari H, Sharififar S, Rahman M, Ansari S, Reynolds BA. Establishing embryonic mouse neural stem cell culture using the neurosphere assay. Vis Exp 2011; p. 47.
[39]
Germain N, Banda E, Grabel L. Embryonic stem cell neurogenesis and neural specification. J Cell Biochem 2010; 111(3): 535-42.
[http://dx.doi.org/10.1002/jcb.22747] [PMID: 20589755]
[40]
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126(4): 663-76.
[http://dx.doi.org/10.1016/j.cell.2006.07.024] [PMID: 16904174]
[41]
Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131(5): 861-72.
[http://dx.doi.org/10.1016/j.cell.2007.11.019] [PMID: 18035408]
[42]
Wernig M, Meissner A, Foreman R, et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 2007; 448(7151): 318-24.
[http://dx.doi.org/10.1038/nature05944] [PMID: 17554336]
[43]
Jung YW, Hysolli E, Kim KY, Tanaka Y, Park IH. Human induced pluripotent stem cells and neurodegenerative disease: Prospects for novel therapies. Curr Opin Neurol 2012; 25(2): 125-30.
[http://dx.doi.org/10.1097/WCO.0b013e3283518226] [PMID: 22357218]
[44]
Bellenchi GC, Volpicelli F, Piscopo V, Perrone-Capano C, di Porzio U. Adult neural stem cells: An endogenous tool to repair brain injury? J Neurochem 2013; 124(2): 159-67.
[http://dx.doi.org/10.1111/jnc.12084] [PMID: 23134340]
[45]
Yoshimura H, Muneta T, Nimura A, Yokoyama A, Koga H, Sekiya I. Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle. Cell Tissue Res 2007; 327(3): 449-62.
[http://dx.doi.org/10.1007/s00441-006-0308-z] [PMID: 17053900]
[46]
Huang JI, Kazmi N, Durbhakula MM, Hering TM, Yoo JU, Johnstone B. Chondrogenic potential of progenitor cells derived from human bone marrow and adipose tissue: A patient-matched comparison. J Orthop Res 2005; 23(6): 1383-9.
[http://dx.doi.org/10.1016/j.orthres.2005.03.008.1100230621] [PMID: 15936917]
[47]
Giusto E, Donegà M, Cossetti C, Pluchino S. Neuro-immune interactions of neural stem cell transplants: From animal disease models to human trials. Exp Neurol 2014; 260(5): 19-32.
[http://dx.doi.org/10.1016/j.expneurol.2013.03.009] [PMID: 23507035]
[48]
Sharp J, Frame J, Siegenthaler M, Nistor G, Keirstead HS. Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants improve recovery after cervical spinal cord injury. Stem Cells 2010; 28(1): 152-63.
[http://dx.doi.org/10.1002/stem.245] [PMID: 19877167]
[49]
Ruff CA, Wilcox JT, Fehlings MG. Cell-based transplantation strategies to promote plasticity following spinal cord injury. Exp Neurol 2012; 235(1): 78-90.
[http://dx.doi.org/10.1016/j.expneurol.2011.02.010] [PMID: 21333647]
[50]
Chen KG, Mallon BS, McKay RDG, Robey PG. Human pluripotent stem cell culture: Considerations for maintenance, expansion, and therapeutics. Cell Stem Cell 2014; 14(1): 13-26.
[http://dx.doi.org/10.1016/j.stem.2013.12.005] [PMID: 24388173]
[51]
Ruzicka J, Machova-Urdzikova L, Gillick J, et al. A comparative study of three different types of stem cells for treatment of rat spinal cord injury. Cell Transplant 2017; 26(4): 585-603.
[http://dx.doi.org/10.3727/096368916X693671] [PMID: 27938489]
[52]
Amoroso MW, Croft GF, Williams DJ, et al. Accelerated high-yield generation of limb-innervating motor neurons from human stem cells. J Neurosci 2013; 33(2): 574-86.
[http://dx.doi.org/10.1523/JNEUROSCI.0906-12.2013] [PMID: 23303937]
[53]
Lukovic D, Diez Lloret A, Stojkovic P, et al. Highly efficient neural conversion of human pluripotent stem cells in adherent and animal-free conditions. Stem Cells Transl Med 2017; 6(4): 1217-26.
[http://dx.doi.org/10.1002/sctm.16-0371] [PMID: 28213969]
[54]
Nutt SE, Chang EA, Suhr ST, et al. Caudalized human iPSC-derived neural progenitor cells produce neurons and glia but fail to restore function in an early chronic spinal cord injury model. Exp Neurol 2013; 248: 491-503.
[http://dx.doi.org/10.1016/j.expneurol.2013.07.010] [PMID: 23891888]
[55]
Kim DS, Lee DR, Kim HS, et al. Highly pure and expandable PSA-NCAM-positive neural precursors from human ESC and iPSC-derived neural rosettes. PLoS One 2012; 7(7), e39715.
[http://dx.doi.org/10.1371/journal.pone.0039715] [PMID: 22911689]
[56]
Zhang Y, Pak C, Han Y, et al. Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron 2013; 78(5): 785-98.
[http://dx.doi.org/10.1016/j.neuron.2013.05.029] [PMID: 23764284]
[57]
Patar A, Dockery P, McMahon S, Howard L. Ex vivo rat transected spinal cord slices as a model to assess lentiviral vector delivery of neurotrophin-3 and short hairpin RNA against NG2. Biology (Basel) 2020; 9(3), E54.
[http://dx.doi.org/10.3390/biology9030054] [PMID: 32183469]
[58]
Abdolahi S, Khodakaram-Tafti A, Aligholi H, et al. Lentiviral vector-mediated transduction of adult neural stem/progenitor cells isolated from the temporal tissues of epileptic patients. Iran J Basic Med Sci 2020; 23(3): 354-61.
[PMID: 32440322]
[59]
Choi HW, Hong YJ, Kim JS, et al. In vivo differentiation of induced pluripotent stem cells into neural stem cells by chimera formation. PLoS One 2017; 12(1), e0170735.
[http://dx.doi.org/10.1371/journal.pone.0170735] [PMID: 28141814]
[60]
Zeng H, Guo M, Martins-Taylor K, et al. Specification of region-specific neurons including forebrain glutamatergic neurons from human induced pluripotent stem cells. PLoS One 2010; 5(7), e11853.
[http://dx.doi.org/10.1371/journal.pone.0011853] [PMID: 20686615]
[61]
Han SS, Williams LA, Eggan KC. Constructing and deconstructing stem cell models of neurological disease. Neuron 2011; 70(4): 626-44.
[http://dx.doi.org/10.1016/j.neuron.2011.05.003] [PMID: 21609821]
[62]
Kim DS, Lee JS, Leem JW, et al. Robust enhancement of neural differentiation from human ES and iPS cells regardless of their innate difference in differentiation propensity. Stem Cell Rev Rep 2010; 6(2): 270-81.
[http://dx.doi.org/10.1007/s12015-010-9138-1] [PMID: 20376579]
[63]
Kitazawa A, Shimizu N. Differentiation of mouse induced pluripotent stem cells into neurons using conditioned medium of dorsal root ganglia. N Biotechnol 2011; 28(4): 326-33.
[http://dx.doi.org/10.1016/j.nbt.2011.03.011] [PMID: 21477670]
[64]
Yang JY, Mumaw JL, Liu Y, Stice SL, West FD. SSEA4-positive pig induced pluripotent stem cells are primed for differentiation into neural cells. Cell Transplant 2013; 22(6): 945-59.
[http://dx.doi.org/10.3727/096368912X657279] [PMID: 23043799]
[65]
Hester ME, Murtha MJ, Song S, et al. Rapid and efficient generation of functional motor neurons from human pluripotent stem cells using gene delivered transcription factor codes. Mol Ther 2011; 19(10): 1905-12.
[http://dx.doi.org/10.1038/mt.2011.135] [PMID: 21772256]
[66]
Reier PJ. Cellular transplantation strategies for spinal cord injury and translational neurobiology. NeuroRx 2004; 1(4): 424-51.
[http://dx.doi.org/10.1602/neurorx.1.4.424] [PMID: 15717046]
[67]
Lepore AC, Walczak P, Rao MS, Fischer I, Bulte JW. MR imaging of lineage-restricted neural precursors following transplantation into the adult spinal cord. Exp Neurol 2006; 201(1): 49-59.
[http://dx.doi.org/10.1016/j.expneurol.2006.03.032] [PMID: 16764862]
[68]
Kong D, Feng B, Amponsah AE, et al. hiPSC-derived NSCs effectively promote the functional recovery of acute spinal cord injury in mice. Stem Cell Res Ther 2021; 12(1): 172.
[http://dx.doi.org/10.1186/s13287-021-02217-9] [PMID: 33706803]
[69]
Okano H, Yamanaka S. iPS cell technologies: Significance and applications to CNS regeneration and disease. Mol Brain 2014; 7(1): 22.
[http://dx.doi.org/10.1186/1756-6606-7-22] [PMID: 24685317]
[70]
Ning L, Hu DL, Tao X, Yu SH. Neural stem cells transplantation for the treatment of spinal cord injury. J Clin Rehabil Tissue Eng Res 2011; 15(10): 1809-13.
[71]
Nori S, Okada Y, Yasuda A, et al. Grafted human-induced pluripotent stem-cell-derived neurospheres promote motor functional recovery after spinal cord injury in mice. Proc Natl Acad Sci USA 2011; 108(40): 16825-30.
[http://dx.doi.org/10.1073/pnas.1108077108] [PMID: 21949375]
[72]
Numasawa-Kuroiwa Y, Okada Y, Shibata S, et al. Involvement of ER stress in dysmyelination of Pelizaeus-Merzbacher Disease with PLP1 missense mutations shown by iPSC-derived oligodendrocytes. Stem Cell Reports 2014; 2(5): 648-61.
[http://dx.doi.org/10.1016/j.stemcr.2014.03.007] [PMID: 24936452]
[73]
Kawabata S, Takano M, Numasawa-Kuroiwa Y, et al. Grafted Human iPS Cell-Derived Oligodendrocyte Precursor Cells Contribute to Robust Remyelination of Demyelinated Axons after Spinal Cord Injury. Stem Cell Reports 2016; 6(1): 1-8.
[http://dx.doi.org/10.1016/j.stemcr.2015.11.013] [PMID: 26724902]
[74]
Lu P, Woodruff G, Wang Y, et al. Long-distance axonal growth from human induced pluripotent stem cells after spinal cord injury. Neuron 2014; 83(4): 789-96.
[http://dx.doi.org/10.1016/j.neuron.2014.07.014] [PMID: 25123310]
[75]
Kobayashi Y, Okada Y, Itakura G, et al. Pre-evaluated safe human iPSC-derived neural stem cells promote functional recovery after spinal cord injury in common marmoset without tumorigenicity. PLoS One 2012; 7(12), e52787.
[http://dx.doi.org/10.1371/journal.pone.0052787] [PMID: 23300777]
[76]
Nori S, Okada Y, Nishimura S, et al. Long-term safety issues of iPSC-based cell therapy in a spinal cord injury model: Oncogenic transformation with epithelial-mesenchymal transition. Stem Cell Reports 2015; 4(3): 360-73.
[http://dx.doi.org/10.1016/j.stemcr.2015.01.006] [PMID: 25684226]
[77]
Iida T, Iwanami A, Sanosaka T, et al. Whole-genome DNA methylation analyses revealed epigenetic instability in tumorigenic human iPS cell-derived neural stem/progenitor cells. Stem Cells 2017; 35(5): 1316-27.
[http://dx.doi.org/10.1002/stem.2581] [PMID: 28142229]
[78]
Okubo T, Iwanami A, Kohyama J, et al. Pretreatment with a γ-secretase inhibitor prevents tumor-like overgrowth in human iPSC-derived transplants for spinal cord injury. Stem Cell Reports 2016; 7(4): 649-63.
[http://dx.doi.org/10.1016/j.stemcr.2016.08.015] [PMID: 27666789]
[79]
Tanimoto Y, Yamasaki T, Nagoshi N, et al. In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell-derived neural stem/progenitor cells transplantation. Stem Cells Transl Med 2020; 9(4): 465-77.
[http://dx.doi.org/10.1002/sctm.19-0150] [PMID: 31904914]
[80]
Kojima K, Miyoshi H, Nagoshi N, et al. Selective ablation of tumorigenic cells following human induced pluripotent stem cell-derived neural stem/progenitor cell transplantation in spinal cord injury. Stem Cells Transl Med 2019; 8(3): 260-70.
[http://dx.doi.org/10.1002/sctm.18-0096] [PMID: 30485733]
[81]
Cheol SJ, Nyun KK, Jeehyun Y, et al. Clinical trial of human fetal brain-derived neural stem/progenitor cell transplantation in patients with traumatic cervical spinal cord injury. Neural Plasticity 2015; 2015: 1-22.
[82]
Levi AD, Okonkwo DO, Park P, et al. Emerging safety of intramedullary transplantation of human neural stem cells in chronic cervical and thoracic spinal cord injury. Neurosurgery 2018; 82(4): 562-75.
[http://dx.doi.org/10.1093/neuros/nyx250] [PMID: 28541431]
[83]
Levi AD, Anderson KD, Okonkwo DO, et al. Clinical outcomes from a multi-center study of human neural stem cell transplantation in chronic cervical spinal cord injury. J Neurotrauma 2019; 36(6): 891-902.
[http://dx.doi.org/10.1089/neu.2018.5843] [PMID: 30180779]
[84]
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.
[http://dx.doi.org/10.1016/j.stem.2018.05.014] [PMID: 29859175]
[85]
Steeves JD, Lammertse D, Curt A, et al. Guidelines for the conduct of clinical trials for spinal cord injury (SCI) as developed by the ICCP panel: Clinical trial outcome measures. Spinal Cord 2007; 45(3): 206-21.
[http://dx.doi.org/10.1038/sj.sc.3102008] [PMID: 17179972]
[86]
Yang Y, Fan Y, Zhang H, et al. Small molecules combined with collagen hydrogel direct neurogenesis and migration of neural stem cells after spinal cord injury. Biomaterials 2021; 269, 120479.
[http://dx.doi.org/10.1016/j.biomaterials.2020.120479] [PMID: 33223332]
[87]
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]
[88]
Liu W, Xu B, Xue W, et al. A functional scaffold to promote the migration and neuronal differentiation of neural stem/progenitor cells for spinal cord injury repair. Biomaterials 2020; 243, 119941.
[http://dx.doi.org/10.1016/j.biomaterials.2020.119941] [PMID: 32172034]
[89]
Xu B, Zhao Y, Xiao Z, et al. A dual functional scaffold tethered with egfr antibody promotes neural stem cell retention and neuronal differentiation for spinal cord injury repair. Adv Healthc Mater 2017; 6(9), 1601279.
[http://dx.doi.org/10.1002/adhm.201601279] [PMID: 28233428]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy