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. 2012 Nov 3;29(1):94–102. doi: 10.1007/s12264-012-1277-8

An update on spinal cord injury research

He-Qi Cao 1,, Er-Dan Dong 1
PMCID: PMC5561853  PMID: 23124646

Abstract

Spinal cord injury (SCI) can have a range of debilitating effects and permanently alter the capabilities and quality of life of survivors. The first specialized centers of care for SCI were established in 1944 and since then an increasing amount of research has been carried out in this area. Despite this, the present treatment and care levels for SCI are not comparable to those in other areas of medicine. In the clinic, the aim of SCI treatment is primarily to limit secondary damage by reducing compression in trauma spots and stabilizing the spinal column. Currently, no effective strategy for functional recovery is offered. In this review, we focus on research progress on the molecular mechanisms underlying SCI, and assess the treatment outcomes of SCI in animal models, i.e., neurotrophins and stem cells are discussed as pre-clinical therapies in animal models. We also assess the resources available and national research projects carried out on SCI in China in recent years, as well as making recommendations for the future allocation of funds in this area.

Keywords: spinal cord injury, neurotrophins, stem cell-based transplantation, research funding

References

  • [1].Devivo M.J. Epidemiology of traumatic spinal cord injury: trends and future implications. Spinal Cord. 2012;50(5):365–372. doi: 10.1038/sc.2011.178. [DOI] [PubMed] [Google Scholar]
  • [2].Qiu J. China spinal cord injury network: changes from within. Lancet Neurol. 2009;8(7):606–607. doi: 10.1016/S1474-4422(09)70162-0. [DOI] [PubMed] [Google Scholar]
  • [3].Charles A.O. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp. 2011;71:281–299. doi: 10.55782/ane-2011-1848. [DOI] [PubMed] [Google Scholar]
  • [4].Rowland J.W., Hawryluk G.W., Kwon B., Fehlings M.G. Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. Neurosurg Focus. 2008;25(5):E2. doi: 10.3171/FOC.2008.25.11.E2. [DOI] [PubMed] [Google Scholar]
  • [5].Akdemir H., Paşaoğlu A., Oztürk F., Selçuklu A., Koç K., Kurtsoy A. Histopathology of experimental spinal cord trauma. Comparison of treatment with TRH, naloxone, and dexamethasone. Res Exp Med (Berl) 1992;192(3):177–183. doi: 10.1007/BF02576273. [DOI] [PubMed] [Google Scholar]
  • [6].Balentine J.D. Pathology of experimental spinal cord trauma. I. The necrotic lesion as a function of vascular injury. Lab Invest. 1978;39(3):236–253. [PubMed] [Google Scholar]
  • [7].Senter H.J., Venes J.L. Altered blood flow and secondary injury in experimental spinal cord trauma. J Neurosurg. 1978;49(4):569–578. doi: 10.3171/jns.1978.49.4.0569. [DOI] [PubMed] [Google Scholar]
  • [8].Fehlings M.G., Tator C.H., Linden R.D. The effect of nimodipine and dextran on axonal function and blood flow following experimental spinal cord injury. J Neurosurg. 1989;71(3):403–416. doi: 10.3171/jns.1989.71.3.0403. [DOI] [PubMed] [Google Scholar]
  • [9].Tator C.H., Fehlings M.G. Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg. 1991;75:15–26. doi: 10.3171/jns.1991.75.1.0015. [DOI] [PubMed] [Google Scholar]
  • [10].Taoka Y., Okajima K., Uchiba M., Murakami K., Harada N., Johno M., et al. Activated protein C reduces the severity of compression-induced spinal cord injury in rats by inhibiting activation of leukocytes. J Neurosci. 1998;18:1393–1398. doi: 10.1523/JNEUROSCI.18-04-01393.1998. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  • [11].Lee S.M., Yune T.Y., Kim S.J., Park D.W., Lee Y.K., Kim Y.C., et al. Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat. J Neurotrauma. 2003;20:1017–1027. doi: 10.1089/089771503770195867. [DOI] [PubMed] [Google Scholar]
  • [12].Cuzzocrea S., Riley D.P., Caputi A.P., Salvemini D. Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacol Rev. 2001;53(1):135–159. [PubMed] [Google Scholar]
  • [13].Xu G.Y., Hughes M.G., Zhang L., Cain L., McAdoo D.J. Administration of glutamate into the spinal cord at extracellular concentrations reached post-injury causes functional impairments. Neurosci Lett. 2005;384(3):271–276. doi: 10.1016/j.neulet.2005.04.100. [DOI] [PubMed] [Google Scholar]
  • [14].Ronaghi M., Erceg S., Moreno-Manzano V., Stojkovic M. Challenges of stem cell therapy for spinal cord injury: human embryonic stem cells, endogenous neural stem cells, or induced pluripotent stem cells? Stem Cells. 2010;28(1):93–99. doi: 10.1002/stem.253. [DOI] [PubMed] [Google Scholar]
  • [15].Schnell L., Fearn S., Klassen H., Schwab M.E., Perry V.H. Acute inflammatory responses to mechanical lesions in the CNS: differences between brain and spinal cord. Eur J Neurosci. 1999;11:3648–3658. doi: 10.1046/j.1460-9568.1999.00792.x. [DOI] [PubMed] [Google Scholar]
  • [16].Bareyre F.M., Schwab M.E. Inflammation, degeneration and regeneration in the injured spinal cord: insights from DNA microarrays. Trends Neurosci. 2003;26(10):555–563. doi: 10.1016/j.tins.2003.08.004. [DOI] [PubMed] [Google Scholar]
  • [17].Oyinbo C.A. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp (Wars) 2011;71(2):281–299. doi: 10.55782/ane-2011-1848. [DOI] [PubMed] [Google Scholar]
  • [18].Lindholm D., Castrén E., Kiefer R., Zafra F., Thoenen H. Transforming growth factor-beta 1 in the rat brain: increase after injury and inhibition of astrocyte proliferation. J Cell Biol. 1992;117(2):395–400. doi: 10.1083/jcb.117.2.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [19].Anderson A.J. Mechanisms and pathways of inflammatory responses in CNS trauma: spinal cord injury. J Spinal Cord Med. 2002;25(2):70–79. doi: 10.1080/10790268.2002.11753604. [DOI] [PubMed] [Google Scholar]
  • [20].Moalem G., Leibowitz-Amit R., Yoles E., Mor F., Cohen I.R., Schwartz M. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat Med. 1999;5(1):49–55. doi: 10.1038/4734. [DOI] [PubMed] [Google Scholar]
  • [21].Moalem G., Gdalyahu A., Shani Y., Otten U., Lazarovici P., Cohen I.R., et al. Production of neurotrophins by activated T cells: implications for neuroprotective autoimmunity. J Autoimmun. 2000;15(3):331–345. doi: 10.1006/jaut.2000.0441. [DOI] [PubMed] [Google Scholar]
  • [22].McTigue D.M. Potential therapeutic targets for PPARgamma after spinal cord injury. PPAR Res. 2008;2008:517162. doi: 10.1155/2008/517162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [23].Hall E.D., Traystman R.J. Role of animal studies in the design of clinical trials. Front Neurol Neurosci. 2009;25:10–33. doi: 10.1159/000209470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [24].Gris P., Tighe A., Levin D., Sharma R., Brown A. Transcriptional regulation of scar gene expression in primary astrocytes. Glia. 2007;55(11):1145–1155. doi: 10.1002/glia.20537. [DOI] [PubMed] [Google Scholar]
  • [25].Liu X.Z., Xu X.M., Hu R., Du C., Zhang S.X., McDonald J.W., et al. Neuronal and glial apoptosis after traumatic spinal cord injury. J Neurosci. 1997;17(14):5395–5406. doi: 10.1523/JNEUROSCI.17-14-05395.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [26].Beattie M.S., Farooqui A.A., Bresnahan J.C. Review of current evidence for apoptosis after spinal cord injury. J Neurotrauma. 2000;17(10):915–925. doi: 10.1089/neu.2000.17.915. [DOI] [PubMed] [Google Scholar]
  • [27].Happel R.D., Smith K.P., Banik N.L., Powers J.M., Hogan E.L., Balentine J.D. Ca2+-accumulation in experimental spinal cord trauma. Brain Res. 1981;211(2):476–479. doi: 10.1016/0006-8993(81)90976-8. [DOI] [PubMed] [Google Scholar]
  • [28].Imaizumi T., Kocsis J.D., Waxman S.G. Anoxic injury in the rat spinal cord: pharmacological evidence for multiple steps in Ca(2+)-dependent injury of the dorsal columns. J Neurotrauma. 1997;14(5):299–311. doi: 10.1089/neu.1997.14.299. [DOI] [PubMed] [Google Scholar]
  • [29].Xiong Y., Rabchevsky A.G., Hall E.D. Role of peroxynitrite in secondary oxidative damage after spinal cord injury. J Neurochem. 2007;100(3):639–649. doi: 10.1111/j.1471-4159.2006.04312.x. [DOI] [PubMed] [Google Scholar]
  • [30].Sullivan P.G., Krishnamurthy S., Patel S.P., Pandya J.D., Rabchevsky A.G. Temporal characterization of mitochondrial bioenergetics after spinal cord injury. J Neurotrauma. 2007;24(6):991–999. doi: 10.1089/neu.2006.0242. [DOI] [PubMed] [Google Scholar]
  • [31].Casha S., Yu W.R., Fehlings M.G. FAS deficiency reduces apoptosis, spares axons and improves function after spinal cord injury. Exp Neurol. 2005;196(2):390–400. doi: 10.1016/j.expneurol.2005.08.020. [DOI] [PubMed] [Google Scholar]
  • [32].Austin J.W., Fehlings M.G. Molecular mechanisms of Fas-mediated cell death in oligodendrocytes. J Neurotrauma. 2008;25(5):411–426. doi: 10.1089/neu.2007.0436. [DOI] [PubMed] [Google Scholar]
  • [33].McCord J.M. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med. 1985;312(3):159–163. doi: 10.1056/NEJM198501173120305. [DOI] [PubMed] [Google Scholar]
  • [34].Wang X., Vaccari J.P., Wang H., Diaz P., German R., Marcillo A.E., et al. Activation of the nuclear factor E2-related factor 2/antioxidant response element pathway is neuroprotective after spinal cord injury. J Neurotrauma. 2012;29(5):936–945. doi: 10.1089/neu.2011.1922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [35].Dumont R.J., Okonkwo D.O., Verma S., Hurlbert R.J., Boulos P.T., Ellegala D.B., et al. Acute spinal cord injury, part I: pathophysiologic mechanisms. Clin Neuropharmacol. 2001;24(5):254–264. doi: 10.1097/00002826-200109000-00002. [DOI] [PubMed] [Google Scholar]
  • [36].Esposito E., Paterniti I., Mazzon E., Genovese T., Galuppo M., Meli R., et al. MK801 attenuates secondary injury in a mouse experimental compression model of spinal cord trauma. MC Neurosci. 2011;12:31. doi: 10.1186/1471-2202-12-31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [37].Simon C.M., Sharif S., Tan R.P., LaPlaca M.C. Spinal cord contusion causes acute plasma membrane damage. J Neurotrauma. 2009;26(4):563–574. doi: 10.1089/neu.2008.0523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [38].Hollis E.R., 2nd, Tuszynski M.H. Neurotrophins: potential therapeutic tools for the treatment of spinal cord injury. Neurotherapeutics. 2011;8(4):694–703. doi: 10.1007/s13311-011-0074-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [39].Bibel M., Barde Y.A. Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev. 2000;14(23):2919–2937. doi: 10.1101/gad.841400. [DOI] [PubMed] [Google Scholar]
  • [40].Grill R.J., Blesch A., Tuszynski M.H. Robust growth of chronically injured spinal cord axons induced by grafts of genetically modified NGF-secreting cells. Exp Neurol. 1997;148(2):444–452. doi: 10.1006/exnr.1997.6704. [DOI] [PubMed] [Google Scholar]
  • [41].Tuszynski M.H., Gabriel K., Gage F.H., Suhr S., Meyer S., Rosetti A. Nerve growth factor delivery by gene transfer induces differential outgrowth of sensory, motor, and noradrenergic neurites after adult spinal cord injury. Exp Neurol. 1996;137(1):157–173. doi: 10.1006/exnr.1996.0016. [DOI] [PubMed] [Google Scholar]
  • [42].Yara T., Kato Y., Kataoka H., Kanchiku T., Suzuki H., Gondo T., et al. Environmental factors involved in axonal regeneration following spinal cord transection in rats. Med Mol Morphol. 2009;42(3):150–154. doi: 10.1007/s00795-009-0454-y. [DOI] [PubMed] [Google Scholar]
  • [43].Mortazavi M.M., Verma K., Deep A., Esfahani F.B., Pritchard P.R., Tubbs R.S., et al. Chemical priming for spinal cord injury: a review of the literature part II-potential therapeutics. Childs Nerv Syst. 2011;27(8):1307–1316. doi: 10.1007/s00381-010-1365-x. [DOI] [PubMed] [Google Scholar]
  • [44].Oudega M., Hagg T. Nerve growth factor promotes regeneration of sensory axons into adult rat spinal cord. Exp Neurol. 1996;140(2):218–229. doi: 10.1006/exnr.1996.0131. [DOI] [PubMed] [Google Scholar]
  • [45].Fumagalli F., Madaschi L., Brenna P., Caffino L., Marfia G., Di Giulio A.M., et al. Single exposure to erythropoietin modulates Nerve Growth Factor expression in the spinal cord following traumatic injury: comparison with methylprednisolone. Eur J Pharmacol. 2008;578(1):19–27. doi: 10.1016/j.ejphar.2007.09.021. [DOI] [PubMed] [Google Scholar]
  • [46].Gwak Y.S., Nam T.S., Paik K.S., Hulsebosch C.E., Leem J.W. Attenuation of mechanical hyperalgesia following spinal cord injury by administration of antibodies to nerve growth factor in the rat. Neuro sci Lett. 2003;336(2):117–120. doi: 10.1016/S0304-3940(02)01251-X. [DOI] [PubMed] [Google Scholar]
  • [47].Krenz N.R., Meakin S.O., Krassioukov A.V., Weaver L.C. Neutralizing intraspinal nerve growth factor blocks autonomic dysreflexia caused by spinal cord injury. J Neurosci. 1999;19(17):7405–7414. doi: 10.1523/JNEUROSCI.19-17-07405.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [48].Novikova L., Novikov L., Kellerth J.O. Brain-derived neurotrophic factor reduces necrotic zone and supports neuronal survival after spinal cord hemisection in adult rats. Neurosci Lett. 1996;220(3):203–206. doi: 10.1016/S0304-3940(96)13267-5. [DOI] [PubMed] [Google Scholar]
  • [49].Vavrek R., Girgis J., Tetzlaff W., Hiebert G.W., Fouad K. BDNF promotes connections of corticospinal neurons onto spared descending interneurons in spinal cord injured rats. Brain. 2006;129Pt6:1534–1545. doi: 10.1093/brain/awl087. [DOI] [PubMed] [Google Scholar]
  • [50].Houweling D.A., van Asseldonk J.T., Lankhorst A.J., Hamers F.P., Martin D., Bär P.R., et al. Local application of collagen containing brain-derived neurotrophic factor decreases the loss of function after spinal cord injury in the adult rat. Neurosci Lett. 1998;251(3):193–196. doi: 10.1016/S0304-3940(98)00536-9. [DOI] [PubMed] [Google Scholar]
  • [51].Ikeda O., Murakami M., Ino H., Yamazaki M., Nemoto T., Koda M., et al. Acute up-regulation of brain-derived neurotrophic factor expression resulting from experimentally induced injury in the rat spinal cord. Acta Neuropathol. 2001;102(3):239–245. doi: 10.1007/s004010000357. [DOI] [PubMed] [Google Scholar]
  • [52].Koda M., Murakami M., Ino H., Yoshinaga K., Ikeda O., Hashimoto M., et al. Brain-derived neurotrophic factor suppresses delayed apoptosis of oligodendrocytes after spinal cord injury in rats. J Neurotrauma. 2002;19(6):777–785. doi: 10.1089/08977150260139147. [DOI] [PubMed] [Google Scholar]
  • [53].Wang Y., Lü G. Repair of spinal cord injury by neural stem cells transfected with brain-derived neurotrophic factor-green fluorescent protein in rats. Neural Regen Res. 2010;5:1303–1307. [Google Scholar]
  • [54].Namiki J., Kojima A., Tator C.H. Effect of brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 on functional recovery and regeneration after spinal cord injury in adult rats. J Neurotrauma. 2000;17(12):1219–1231. doi: 10.1089/neu.2000.17.1219. [DOI] [PubMed] [Google Scholar]
  • [55].Kim D.H., Jahng T.A. Continuous brain-derived neurotrophic factor (BDNF) infusion after methylprednisolone treatment in severe spinal cord injury. J Korean Med Sci. 2004;19(1):113–122. doi: 10.3346/jkms.2004.19.1.113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [56].Zhou L., Baumgartner B.J., Hill-Felberg S.J., McGowen L.R., Shine H.D. Neurotrophin-3 expressed in situ induces axonal plasticity in the adult injured spinal cord. J Neurosci. 2003;23(4):1424–1431. doi: 10.1523/JNEUROSCI.23-04-01424.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [57].Schnell L., Schneider R., Kolbeck R., Barde Y.A., Schwab M.E. Neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesion. Nature. 1994;367(6459):170–173. doi: 10.1038/367170a0. [DOI] [PubMed] [Google Scholar]
  • [58].Kusano K., Enomoto M., Hirai T., Tsoulfas P., Sotome S., Shinomiya K., et al. Transplanted neural progenitor cells expressing mutant NT3 promote myelination and partial hindlimb recovery in the chronic phase after spinal cord injury. Biochem Biophys Res Commun. 2010;393(4):812–817. doi: 10.1016/j.bbrc.2010.02.088. [DOI] [PubMed] [Google Scholar]
  • [59].Mortazavi M.M., Verma K., Tubbs R.S., Theodore N. Cellular and paracellular transplants for spinal cord injury: a review of the literature. Childs Nerv Syst. 2011;27(2):237–243. doi: 10.1007/s00381-010-1312-x. [DOI] [PubMed] [Google Scholar]
  • [60].Eftekharpour E., Karimi-Abdolrezaee S., Fehlings M.G. Current status of experimental cell replacement approaches to spinal cord injury. Neurosurg Focus. 2008;24(3–4):E19. doi: 10.3171/FOC/2008/24/3-4/E18. [DOI] [PubMed] [Google Scholar]
  • [61].Stangel M., Hartung H.P. Remyelinating strategies for the treatment of multiple sclerosis. Prog Neurobiol. 2002;68(5):361–376. doi: 10.1016/S0301-0082(02)00105-3. [DOI] [PubMed] [Google Scholar]
  • [62].Erceg S., Ronaghi M., Stojković M. Human embryonic stem cell differentiation toward regional specific neural precursors. Stem Cells. 2009;27(1):78–87. doi: 10.1634/stemcells.2008-0543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [63].Lee H., Shamy G.A., Elkabetz Y., Schofield C.M., Harrsion N.L., Panagiotakos G., et al. Directed differentiation and transplantation of human embryonic stem cell-derived motoneurons. Stem Cells. 2007;25(8):1931–1939. doi: 10.1634/stemcells.2007-0097. [DOI] [PubMed] [Google Scholar]
  • [64].Nistor G.I., Totoiu M.O., Haque N., Carpenter M.K., Keirstead H.S. Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation. Glia. 2005;49(3):385–396. doi: 10.1002/glia.20127. [DOI] [PubMed] [Google Scholar]
  • [65].Rossant J. Stem cells and early lineage development. Cell. 2008;132(4):527–531. doi: 10.1016/j.cell.2008.01.039. [DOI] [PubMed] [Google Scholar]
  • [66].Yang D., Zhang Z.J., Oldenburg M., Ayala M., Zhang S.C. Human embryonic stem cell-derived dopaminergic neurons reverse functional deficit in parkinsonian rats. Stem Cells. 2008;26(1):55–63. doi: 10.1634/stemcells.2007-0494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [67].Aharonowiz M., Einstein O., Fainstein N., Lassmann H., Reubinoff B., Ben-Hur T. Neuroprotective effect of transplanted human embryonic stem cell-derived neural precursors in an animal model of multiple sclerosis. PLoS One. 2008;3(9):e3145. doi: 10.1371/journal.pone.0003145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [68].Glazova M., Pak E.S., Moretto J., Hollis S., Brewer K.L., Murashov A.K. Pre-differentiated embryonic stem cells promote neuronal regeneration by cross-coupling of BDNF and IL-6 signaling pathways in the host tissue. J Neurotrauma. 2009;26(7):1029–1042. doi: 10.1089/neu.2008.0785. [DOI] [PubMed] [Google Scholar]
  • [69].Salewski R.P., Eftekharpour E., Fehlings M.G. Are induced pluripotent stem cells the future of cell-based regenerative therapies for spinal cord injury? J Cell Physiol. 2010;222(3):515–521. doi: 10.1002/jcp.21995. [DOI] [PubMed] [Google Scholar]
  • [70].Cattaneo E., McKay R. Proliferation and differentiation of neuronal stem cells regulated by nerve growth factor. Nature. 1990;347(6295):762–765. doi: 10.1038/347762a0. [DOI] [PubMed] [Google Scholar]
  • [71].Hsu Y.C., Lee D.C., Chiu I.M. Neural stem cells, neural progenitors, and neurotrophic factors. Cell Transplant. 2007;16(2):133–150. [PubMed] [Google Scholar]
  • [72].Shihabuddin L.S., Horner P.J., Ray J., Gage F.H. Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus. J Neurosci. 2000;20(23):8727–8735. doi: 10.1523/JNEUROSCI.20-23-08727.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [73].Fricker R.A., Carpenter M.K., Winkler C., Greco C., Gates M.A., Björklund A. Site-specific migration and neuronal differentiation of human neural progenitor cells after transplantation in the adult rat brain. J Neurosci. 1999;19(14):5990–6005. doi: 10.1523/JNEUROSCI.19-14-05990.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [74].Cao Q.L., Zhang Y.P., Howard R.M., Walters W.M., Tsoulfas P., Whittemore S.R. Pluripotent stem cells engrafted into the normal or lesioned adult rat spinal cord are restricted to a glial lineage. Exp Neurol. 2001;167(1):48–58. doi: 10.1006/exnr.2000.7536. [DOI] [PubMed] [Google Scholar]
  • [75].Karimi-Abdolrezaee S., Eftekharpour E., Wang J., Morshead C.M., Fehlings M.G. Delayed transplantation of adult neural precursor cells promotes remyelination and functional neurological recovery after spinal cord injury. J Neurosci. 2006;26(13):3377–3389. doi: 10.1523/JNEUROSCI.4184-05.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [76].Seaberg R.M., van der Kooy D. Adult rodent neurogenic regions: the ventricular subependyma contains neural stem cells, but the dentate gyrus contains restricted progenitors. J Neurosci. 2002;22(5):1784–1793. doi: 10.1523/JNEUROSCI.22-05-01784.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [77].Totoiu M.O., Keirstead H.S. Spinal cord injury is accompanied by chronic progressive demyelination. J Comp Neurol. 2005;486(4):373–383. doi: 10.1002/cne.20517. [DOI] [PubMed] [Google Scholar]
  • [78].Eftekharpour E., Karimi-Abdolrezaee S., Wang J., El Beheiry H., Morshead C., Fehlings M.G. Myelination of congenitally dysmyelinated spinal cord axons by adult neural precursor cells results in formation of nodes of Ranvier and improved axonal conduction. J Neurosci. 2007;27(13):3416–3428. doi: 10.1523/JNEUROSCI.0273-07.2007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [79].Coutts M., Keirstead H.S. Stem cells for the treatment of spinal cord injury. Exp Neurol. 2008;209(2):368–377. doi: 10.1016/j.expneurol.2007.09.002. [DOI] [PubMed] [Google Scholar]
  • [80].Davies J.E., Huang C., Proschel C., Noble M., Mayer-Proschel M., Davies S.J. Astrocytes derived from glial-restricted precursors promote spinal cord repair. J Biol. 2006;5(3):7. doi: 10.1186/jbiol35. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [81].Kim B.G., Hwang D.H., Lee S.I., Kim E.J., Kim S.U. Stem cellbased cell therapy for spinal cord injury. Cell Transplant. 2007;16(4):355–364. doi: 10.3727/000000007783464885. [DOI] [PubMed] [Google Scholar]
  • [82].Zhu J., Wu X., Zhang H.L. Adult neural stem cell therapy: expansion in vitro, tracking in vivo and clinical transplantation. Curr Drug Targets. 2005;6(1):97–110. doi: 10.2174/1389450053345055. [DOI] [PubMed] [Google Scholar]
  • [83].Dimos J.T., Rodolfa K.T., Niakan K.K., Weisenthal L.M., Mitsumoto H., Chung W., et al. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science. 2008;321(5893):1218–1221. doi: 10.1126/science.1158799. [DOI] [PubMed] [Google Scholar]
  • [84].Wernig M., Zhao J.P., Pruszak J., Hedlund E., Fu D., Soldner F., et al. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc Natl Acad Sci U S A. 2008;105(15):5856–5861. doi: 10.1073/pnas.0801677105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [85].Takahashi K., Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–676. doi: 10.1016/j.cell.2006.07.024. [DOI] [PubMed] [Google Scholar]
  • [86].Liu H., Zhu F., Yong J., Zhang P., Hou P., Li H., et al. Generation of induced pluripotent stem cells from adult rhesus monkey fibroblasts. Cell Stem Cell. 2008;3(6):587–590. doi: 10.1016/j.stem.2008.10.014. [DOI] [PubMed] [Google Scholar]
  • [87].Liao J., Cui C., Chen S., Ren J., Chen J., Gao Y., et al. Generation of induced pluripotent stem cell lines from adult rat cells. Cell Stem Cell. 2009;4(1):11–15. doi: 10.1016/j.stem.2008.11.013. [DOI] [PubMed] [Google Scholar]
  • [88].Takahashi K., Tanabe K., Ohnuki M., Narita M., Ichisaka T., Tomoda K., et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861–872. doi: 10.1016/j.cell.2007.11.019. [DOI] [PubMed] [Google Scholar]
  • [89].Yu J., Vodyanik M.A., Smuga-Otto K., Antosiewicz-Bourget J., Frane J.L., Tian S., et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318(5858):1917–1920. doi: 10.1126/science.1151526. [DOI] [PubMed] [Google Scholar]
  • [90].Lowry W.E., Richter L., Yachechko R., Pyle A.D., Tchieu J., Sridharan R., et al. Generation of human induced pluripotent stem cells from dermal fibroblasts. Proc Natl Acad Sci U S A. 2008;105(8):2883–2888. doi: 10.1073/pnas.0711983105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [91].Park I.H., Zhao R., West J.A., Yabuuchi A., Huo H., Ince T.A., et al. Reprogramming of human somatic cells to pluripotency with defined factors. Nature. 2008;451(7175):141–146. doi: 10.1038/nature06534. [DOI] [PubMed] [Google Scholar]
  • [92].Yamanaka S. A fresh look at iPS cells. Cell. 2009;137(1):13–17. doi: 10.1016/j.cell.2009.03.034. [DOI] [PubMed] [Google Scholar]
  • [93].Tsuji O., Miura K., Fujiyoshi K., Momoshima S., Nakamura M., Okano H. Cell therapy for spinal cord injury by neural stem/ progenitor cells derived from iPS/ES cells. Neurotherapeutics. 2011;8(4):668–676. doi: 10.1007/s13311-011-0063-z. [DOI] [PMC free article] [PubMed] [Google Scholar]

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