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Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury

Abstract

Transplantation of bone marrow-derived mesenchymal stromal cells (MSCs) into the injured brain or spinal cord may provide therapeutic benefit. Several models of central nervous system (CNS) injury have been examined, including that of ischemic stroke, traumatic brain injury and traumatic spinal cord injury in rodent, primate and, more recently, human trials. Although it has been suggested that differentiation of MSCs into cells of neural lineage may occur both in vitro and in vivo, this is unlikely to be a major factor in functional recovery after brain or spinal cord injury. Other mechanisms of recovery that may play a role include neuroprotection, creation of a favorable environment for regeneration, expression of growth factors or cytokines, vascular effects or remyelination. These mechanisms are not mutually exclusive, and it is likely that more than one contribute to functional recovery. In light of the uncertainty surrounding the fate and mechanism of action of MSCs transplanted into the CNS, further preclinical studies with appropriate animal models are urgently needed to better inform the design of new clinical trials.

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References

  1. Karimi-Abdolrezaee S, Eftekharpour E, Wang J, Morshead CM, Fehlings MG . Delayed transplantation of adult neural precursor cells promotes remyelination and functional neurological recovery after spinal cord injury. J Neurosci 2006; 26: 3377–3389.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kokai LE, Rubin JP, Marra KG . The potential of adipose-derived adult stem cells as a source of neuronal progenitor cells. Plast Reconstr Surg 2005; 116: 1453–1460.

    Article  CAS  PubMed  Google Scholar 

  3. McDonald JW, Liu XZ, Qu Y, Liu S, Mickey SK, Turetsky D et al. Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nat Med 1999; 5: 1410–1412.

    Article  CAS  PubMed  Google Scholar 

  4. Teng YD, Lavik EB, Qu X, Park KI, Ourednik J, Zurakowski D et al. Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proc Natl Acad Sci USA 2002; 99: 3024–3029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Koshizuka S, Okada S, Okawa A, Koda M, Murasawa M, Hashimoto M et al. Transplanted hematopoietic stem cells from bone marrow differentiate into neural lineage cells and promote functional recovery after spinal cord injury in mice. J Neuropathol Exp Neurol 2004; 63: 64–72.

    Article  PubMed  Google Scholar 

  6. Tator CH . Review of treatment trials in human spinal cord injury: issues, difficulties, and recommendations. Neurosurgery 2006; 59: 957–982; discussion 982–987.

    Article  PubMed  Google Scholar 

  7. Horwitz EM, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini FC et al. Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy 2005; 7: 393–395.

    Article  CAS  PubMed  Google Scholar 

  8. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143–147.

    Article  CAS  PubMed  Google Scholar 

  9. Dormady SP, Bashayan O, Dougherty R, Zhang XM, Basch RS . Immortalized multipotential mesenchymal cells and the hematopoietic microenvironment. J Hematother Stem Cell Res 2001; 10: 125–140.

    Article  CAS  PubMed  Google Scholar 

  10. Rojas M, Xu J, Woods CR, Mora AL, Spears W, Roman J et al. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol 2005; 33: 145–152.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ferrari G, Cusella-De Angelis G, Coletta M, Paolucci E, Stornaiuolo A, Cossu G et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 1998; 279: 1528–1530.

    Article  CAS  PubMed  Google Scholar 

  12. Keating A . Mesenchymal stromal cells. Curr Opin Hematol 2006; 13: 419–425.

    Article  PubMed  Google Scholar 

  13. Irons H, Lind JG, Wakade CG, Yu G, Hadman M, Carroll J et al. Intracerebral xenotransplantation of GFP mouse bone marrow stromal cells in intact and stroke rat brain: graft survival and immunologic response. Cell Transplant 2004; 13: 283–294.

    Article  CAS  PubMed  Google Scholar 

  14. Swanger SA, Neuhuber B, Himes BT, Bakshi A, Fischer I . Analysis of allogeneic and syngeneic bone marrow stromal cell graft survival in the spinal cord. Cell Transplant 2005; 14: 775–786.

    Article  PubMed  Google Scholar 

  15. Coyne TM, Akiva JM, Woodbury D, Black IB . Marrow stromal cells transplanted to the adult brain are rejected by an inflammatory response and transfer donor labels to host neurons and glia. Stem Cells 2006; 24: 2483–2492.

    Article  PubMed  Google Scholar 

  16. Woodbury D, Schwarz EJ, Prockop DJ, Black IB . Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 2000; 61: 364–370.

    Article  CAS  PubMed  Google Scholar 

  17. Black IB, Woodbury D . Adult rat and human bone marrow stromal stem cells differentiate into neurons. Blood Cells Mol Dis 2001; 27: 632–636.

    Article  CAS  PubMed  Google Scholar 

  18. Woodbury D, Reynolds K, Black IB . Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis. J Neurosci Res 2002; 69: 908–917.

    Article  CAS  PubMed  Google Scholar 

  19. Munoz-Elias G, Woodbury D, Black IB . Marrow stromal cells, mitosis, and neuronal differentiation: stem cell and precursor functions. Stem Cells 2003; 21: 437–448.

    Article  PubMed  Google Scholar 

  20. Phinney DG, Isakova I . Plasticity and therapeutic potential of mesenchymal stem cells in the nervous system. Curr Pharm Des 2005; 11: 1255–1265.

    Article  CAS  PubMed  Google Scholar 

  21. Deng W, Obrocka M, Fischer I, Prockop DJ . In vitro differentiation of human marrow stromal cells into early progenitors of neural cells by conditions that increase intracellular cyclic AMP. Biochem Biophys Res Commun 2001; 282: 148–152.

    Article  CAS  PubMed  Google Scholar 

  22. Rismanchi N, Floyd CL, Berman RF, Lyeth BG . Cell death and long-term maintenance of neuron-like state after differentiation of rat bone marrow stromal cells: a comparison of protocols. Brain Res 2003; 991: 46–55.

    Article  CAS  PubMed  Google Scholar 

  23. Vallieres L, Sawchenko PE . Bone marrow-derived cells that populate the adult mouse brain preserve their hematopoietic identity. J Neurosci 2003; 23: 5197–5207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Massengale M, Wagers AJ, Vogel H, Weissman IL . Hematopoietic cells maintain hematopoietic fates upon entering the brain. J Exp Med 2005; 201: 1579–1589.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Munoz-Elias G, Marcus AJ, Coyne TM, Woodbury D, Black IB . Adult bone marrow stromal cells in the embryonic brain: engraftment, migration, differentiation, and long-term survival. J Neurosci 2004; 24: 4585–4595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sigurjonsson OE, Perreault MC, Egeland T, Glover JC . Adult human hematopoietic stem cells produce neurons efficiently in the regenerating chicken embryo spinal cord. Proc Natl Acad Sci USA 2005; 102: 5227–5232.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Neuhuber B, Gallo G, Howard L, Kostura L, Mackay A, Fischer I . Reevaluation of in vitro differentiation protocols for bone marrow stromal cells: disruption of actin cytoskeleton induces rapid morphological changes and mimics neuronal phenotype. J Neurosci Res 2004; 77: 192–204.

    Article  CAS  PubMed  Google Scholar 

  28. Lu P, Blesch A, Tuszynski MH . Induction of bone marrow stromal cells to neurons: differentiation, transdifferentiation, or artifact? J Neurosci Res 2004; 77: 174–191.

    Article  CAS  PubMed  Google Scholar 

  29. Suon S, Jin H, Donaldson AE, Caterson EJ, Tuan RS, Deschennes G et al. Transient differentiation of adult human bone marrow cells into neuron-like cells in culture: development of morphological and biochemical traits is mediated by different molecular mechanisms. Stem Cells Dev 2004; 13: 625–635.

    Article  CAS  PubMed  Google Scholar 

  30. Castro RF, Jackson KA, Goodell MA, Robertson CS, Liu H, Shine HD . Failure of bone marrow cells to transdifferentiate into neural cells in vivo. Science 2002; 297: 1299.

    Article  CAS  PubMed  Google Scholar 

  31. Nan Z, Grande A, Sanberg CD, Sanberg PR, Low WC . Infusion of human umbilical cord blood ameliorates neurologic deficits in rats with hemorrhagic brain injury. Ann N Y Acad Sci 2005; 1049: 84–96.

    Article  PubMed  Google Scholar 

  32. Peterson DA . Umbilical cord blood cells and brain stroke injury: bringing in fresh blood to address an old problem. J Clin Invest 2004; 114: 312–314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Willing AE, Lixian J, Milliken M, Poulos S, Zigova T, Song S et al. Intravenous versus intrastriatal cord blood administration in a rodent model of stroke. J Neurosci Res 2003; 73: 296–307.

    Article  CAS  PubMed  Google Scholar 

  34. Willing AE, Vendrame M, Mallery J, Cassady CJ, Davis CD, Sanchez-Ramos J et al. Mobilized peripheral blood cells administered intravenously produce functional recovery in stroke. Cell Transplant 2003; 12: 449–454.

    Article  PubMed  Google Scholar 

  35. Kang SK, Lee DH, Bae YC, Kim HK, Baik SY, Jung JS . Improvement of neurological deficits by intracerebral transplantation of human adipose tissue-derived stromal cells after cerebral ischemia in rats. Exp Neurol 2003; 183: 355–366.

    Article  CAS  PubMed  Google Scholar 

  36. Chen J, Li Y, Chopp M . Intracerebral transplantation of bone marrow with BDNF after MCAo in rat. Neuropharmacology 2000; 39: 711–716.

    Article  CAS  PubMed  Google Scholar 

  37. Chopp M, Li Y . Treatment of neural injury with marrow stromal cells. Lancet Neurol 2002; 1: 92–100.

    Article  PubMed  Google Scholar 

  38. Mahmood A, Lu D, Wang L, Chopp M . Intracerebral transplantation of marrow stromal cells cultured with neurotrophic factors promotes functional recovery in adult rats subjected to traumatic brain injury. J Neurotrauma 2002; 19: 1609–1617.

    Article  PubMed  Google Scholar 

  39. Mahmood A, Lu D, Chopp M . Intravenous administration of marrow stromal cells (MSCs) increases the expression of growth factors in rat brain after traumatic brain injury. J Neurotrauma 2004; 21: 33–39.

    Article  PubMed  Google Scholar 

  40. Mahmood A, Lu D, Chopp M . Marrow stromal cell transplantation after traumatic brain injury promotes cellular proliferation within the brain. Neurosurgery 2004; 55: 1185–1193.

    Article  PubMed  Google Scholar 

  41. Mahmood A, Lu D, Qu C, Goussev A, Chopp M . Long-term recovery after bone marrow stromal cell treatment of traumatic brain injury in rats. J Neurosurg 2006; 104: 272–277.

    Article  PubMed  Google Scholar 

  42. Hu DZ, Zhou LF, Zhu JH . Marrow stromal cells administrated intracisternally to rats after traumatic brain injury migrate into the brain and improve neurological function. Chin Med J (Engl) 2004; 117: 1576–1578.

    Google Scholar 

  43. Hu DZ, Zhou LF, Zhu J, Mao Y, Wu XH . Upregulated gene expression of local brain-derived neurotrophic factor and nerve growth factor after intracisternal administration of marrow stromal cells in rats with traumatic brain injury. Chin J Traumatol 2005; 8: 23–26.

    CAS  PubMed  Google Scholar 

  44. Chen Q, Long Y, Yuan X, Zou L, Sun J, Chen S et al. Protective effects of bone marrow stromal cell transplantation in injured rodent brain: synthesis of neurotrophic factors. J Neurosci Res 2005; 80: 611–619.

    Article  CAS  PubMed  Google Scholar 

  45. Borlongan CV, Lind JG, Dillon-Carter O, Yu G, Hadman M, Cheng C et al. Intracerebral xenografts of mouse bone marrow cells in adult rats facilitate restoration of cerebral blood flow and blood–brain barrier. Brain Res 2004; 1009: 26–33.

    Article  CAS  PubMed  Google Scholar 

  46. Lu J, Moochhala S, Moore XL, Ng KC, Tan MH, Lee LK et al. Adult bone marrow cells differentiate into neural phenotypes and improve functional recovery in rats following traumatic brain injury. Neurosci Lett 2006; 398: 12–17.

    Article  CAS  PubMed  Google Scholar 

  47. Borlongan CV, Lind JG, Dillon-Carter O, Yu G, Hadman M, Cheng C et al. Bone marrow grafts restore cerebral blood flow and blood brain barrier in stroke rats. Brain Res 2004; 1010: 108–116.

    Article  CAS  PubMed  Google Scholar 

  48. Mahmood A, Lu D, Lu M, Chopp M . Treatment of traumatic brain injury in adult rats with intravenous administration of human bone marrow stromal cells. Neurosurgery 2003; 53: 697–702; discussion 702–703.

    Article  PubMed  Google Scholar 

  49. Mahmood A, Lu D, Qu C, Goussev A, Chopp M . Human marrow stromal cell treatment provides long-lasting benefit after traumatic brain injury in rats. Neurosurgery 2005; 57: 1026–1031; discussion 1026–1031.

    Article  PubMed  Google Scholar 

  50. Gao Q, Katakowski M, Chen X, Li Y, Chopp M . Human marrow stromal cells enhance connexin43 gap junction intercellular communication in cultured astrocytes. Cell Transplant 2005; 14: 109–117.

    Article  PubMed  Google Scholar 

  51. Eglitis MA, Dawson D, Park KW, Mouradian MM . Targeting of marrow-derived astrocytes to the ischemic brain. Neuroreport 1999; 10: 1289–1292.

    Article  CAS  PubMed  Google Scholar 

  52. Li Y, Chopp M, Chen J, Wang L, Gautam SC, Xu YX et al. Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice. J Cereb Blood Flow Metab 2000; 20: 1311–1319.

    Article  CAS  PubMed  Google Scholar 

  53. Chen J, Li Y, Katakowski M, Chen X, Wang L, Lu D et al. Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat. J Neurosci Res 2003; 73: 778–786.

    Article  CAS  PubMed  Google Scholar 

  54. Shen LH, Li Y, Chen J, Zacharek A, Gao Q, Kapke A et al. Therapeutic benefit of bone marrow stromal cells administered 1 month after stroke. J Cereb Blood Flow Metab 2006; 27: 6–13.

    Article  PubMed  CAS  Google Scholar 

  55. Shen LH, Li Y, Chen J, Zhang J, Vanguri P, Borneman J et al. Intracarotid transplantation of bone marrow stromal cells increases axon-myelin remodeling after stroke. Neuroscience 2006; 137: 393–399.

    Article  CAS  PubMed  Google Scholar 

  56. Li Y, Chen J, Zhang CL, Wang L, Lu D, Katakowski M et al. Gliosis and brain remodeling after treatment of stroke in rats with marrow stromal cells. Glia 2005; 49: 407–417.

    Article  PubMed  Google Scholar 

  57. Lee J, Kuroda S, Shichinohe H, Ikeda J, Seki T, Hida K et al. Migration and differentiation of nuclear fluorescence-labeled bone marrow stromal cells after transplantation into cerebral infarct and spinal cord injury in mice. Neuropathology 2003; 23: 169–180.

    Article  PubMed  Google Scholar 

  58. Yano S, Kuroda S, Shichinohe H, Hida K, Iwasaki Y . Do bone marrow stromal cells proliferate after transplantation into mice cerebral infarct? – a double labeling study. Brain Res 2005; 1065: 60–67.

    Article  CAS  PubMed  Google Scholar 

  59. Shichinohe H, Kuroda S, Yano S, Ohnishi T, Tamagami H, Hida K et al. Improved expression of gamma-aminobutyric acid receptor in mice with cerebral infarct and transplanted bone marrow stromal cells: an autoradiographic and histologic analysis. J Nucl Med 2006; 47: 486–491.

    CAS  PubMed  Google Scholar 

  60. Ikeda N, Nonoguchi N, Zhao MZ, Watanabe T, Kajimoto Y, Furutama D et al. Bone marrow stromal cells that enhanced fibroblast growth factor-2 secretion by herpes simplex virus vector improve neurological outcome after transient focal cerebral ischemia in rats. Stroke 2005; 36: 2725–2730.

    Article  CAS  PubMed  Google Scholar 

  61. Zhao MZ, Nonoguchi N, Ikeda N, Watanabe T, Furutama D, Miyazawa D et al. Novel therapeutic strategy for stroke in rats by bone marrow stromal cells and ex vivo HGF gene transfer with HSV-1 vector. J Cereb Blood Flow Metab 2006; 26: 1176–1188.

    Article  CAS  PubMed  Google Scholar 

  62. Gao Q, Li Y, Chopp M . Bone marrow stromal cells increase astrocyte survival via upregulation of phosphoinositide 3-kinase/threonine protein kinase and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways and stimulate astrocyte trophic factor gene expression after anaerobic insult. Neuroscience 2005; 136: 123–134.

    Article  CAS  PubMed  Google Scholar 

  63. Zhang J, Li Y, Chen J, Yang M, Katakowski M, Lu M et al. Expression of insulin-like growth factor 1 and receptor in ischemic rats treated with human marrow stromal cells. Brain Res 2004; 1030: 19–27.

    Article  CAS  PubMed  Google Scholar 

  64. Song S, Kamath S, Mosquera D, Zigova T, Sanberg P, Vesely DL et al. Expression of brain natriuretic peptide by human bone marrow stromal cells. Exp Neurol 2004; 185: 191–197.

    Article  CAS  PubMed  Google Scholar 

  65. Chen X, Li Y, Wang L, Katakowski M, Zhang L, Chen J et al. Ischemic rat brain extracts induce human marrow stromal cell growth factor production. Neuropathology 2002; 22: 275–279.

    Article  PubMed  Google Scholar 

  66. Kinnaird T, Stabile E, Burnett MS, Lee CW, Barr S, Fuchs S et al. Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res 2004; 94: 678–685.

    Article  CAS  PubMed  Google Scholar 

  67. Zhang J, Li Y, Chen J, Cui Y, Lu M, Elias SB et al. Human bone marrow stromal cell treatment improves neurological functional recovery in EAE mice. Exp Neurol 2005; 195: 16–26.

    Article  CAS  PubMed  Google Scholar 

  68. Uccelli A, Zappia E, Benvenuto F, Frassoni F, Mancardi G . Stem cells in inflammatory demyelinating disorders: a dual role for immunosuppression and neuroprotection. Expert Opin Biol Ther 2006; 6: 17–22.

    Article  CAS  PubMed  Google Scholar 

  69. Kurozumi K, Nakamura K, Tamiya T, Kawano Y, Kobune M, Hirai S et al. BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model. Mol Ther 2004; 9: 189–197.

    Article  CAS  PubMed  Google Scholar 

  70. Chen J, Li Y, Zhang R, Katakowski M, Gautam SC, Xu Y et al. Combination therapy of stroke in rats with a nitric oxide donor and human bone marrow stromal cells enhances angiogenesis and neurogenesis. Brain Res 2004; 1005: 21–28.

    Article  CAS  PubMed  Google Scholar 

  71. Yano S, Kuroda S, Lee JB, Shichinohe H, Seki T, Ikeda J et al. In vivo fluorescence tracking of bone marrow stromal cells transplanted into a pneumatic injury model of rat spinal cord. J Neurotrauma 2005; 22: 907–918.

    Article  PubMed  Google Scholar 

  72. Koda M, Okada S, Nakayama T, Koshizuka S, Kamada T, Nishio Y et al. Hematopoietic stem cell and marrow stromal cell for spinal cord injury in mice. Neuroreport 2005; 16: 1763–1767.

    Article  PubMed  Google Scholar 

  73. Sykova E, Jendelova P . Magnetic resonance tracking of implanted adult and embryonic stem cells in injured brain and spinal cord. Ann N Y Acad Sci 2005; 1049: 146–160.

    Article  PubMed  Google Scholar 

  74. Chopp M, Zhang XH, Li Y, Wang L, Chen J, Lu D et al. Spinal cord injury in rat: treatment with bone marrow stromal cell transplantation. Neuroreport 2000; 11: 3001–3005.

    Article  CAS  PubMed  Google Scholar 

  75. Wu S, Suzuki Y, Ejiri Y, Noda T, Bai H, Kitada M et al. Bone marrow stromal cells enhance differentiation of cocultured neurosphere cells and promote regeneration of injured spinal cord. J Neurosci Res 2003; 72: 343–351.

    Article  CAS  PubMed  Google Scholar 

  76. Hofstetter CP, Schwarz EJ, Hess D, Widenfalk J, El Manira A, Prockop DJ et al. Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc Natl Acad Sci USA 2002; 99: 2199–2204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Zurita M, Vaquero J . Bone marrow stromal cells can achieve cure of chronic paraplegic rats: functional and morphological outcome one year after transplantation. Neurosci Lett 2006; 402: 51–56.

    Article  CAS  PubMed  Google Scholar 

  78. Zurita M, Vaquero J . Functional recovery in chronic paraplegia after bone marrow stromal cells transplantation. Neuroreport 2004; 15: 1105–1108.

    Article  PubMed  Google Scholar 

  79. Ankeny DP, McTigue DM, Jakeman LB . Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord injury in rats. Exp Neurol 2004; 190: 17–31.

    Article  PubMed  Google Scholar 

  80. Sasaki M, Honmou O, Akiyama Y, Uede T, Hashi K, Kocsis JD . Transplantation of an acutely isolated bone marrow fraction repairs demyelinated adult rat spinal cord axons. Glia 2001; 35: 26–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Akiyama Y, Radtke C, Honmou O, Kocsis JD . Remyelination of the spinal cord following intravenous delivery of bone marrow cells. Glia 2002; 39: 229–236.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Akiyama Y, Radtke C, Kocsis JD . Remyelination of the rat spinal cord by transplantation of identified bone marrow stromal cells. J Neurosci 2002; 22: 6623–6630.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Ohta M, Suzuki Y, Noda T, Ejiri Y, Dezawa M, Kataoka K et al. Bone marrow stromal cells infused into the cerebrospinal fluid promote functional recovery of the injured rat spinal cord with reduced cavity formation. Exp Neurol 2004; 187: 266–278.

    Article  CAS  PubMed  Google Scholar 

  84. Bakshi A, Barshinger AL, Swanger SA, Madhavani V, Shumsky JS, Neuhuber B et al. Lumbar puncture delivery of bone marrow stromal cells in spinal cord contusion: a novel method for minimally invasive cell transplantation. J Neurotrauma 2006; 23: 55–65.

    Article  PubMed  Google Scholar 

  85. de Haro J, Zurita M, Ayllon L, Vaquero J . Detection of 111In-oxine-labeled bone marrow stromal cells after intravenous or intralesional administration in chronic paraplegic rats. Neurosci Lett 2005; 377: 7–11.

    Article  CAS  PubMed  Google Scholar 

  86. Vaquero J, Zurita M, Oya S, Santos M . Cell therapy using bone marrow stromal cells in chronic paraplegic rats: systemic or local administration? Neurosci Lett 2006; 398: 129–134.

    Article  CAS  PubMed  Google Scholar 

  87. Kamada T, Koda M, Dezawa M, Yoshinaga K, Hashimoto M, Koshizuka S et al. Transplantation of bone marrow stromal cell-derived Schwann cells promotes axonal regeneration and functional recovery after complete transection of adult rat spinal cord. J Neuropathol Exp Neurol 2005; 64: 37–45.

    Article  PubMed  Google Scholar 

  88. Deng YB, Yuan QT, Liu XG, Liu XL, Liu Y, Liu ZG et al. Functional recovery after rhesus monkey spinal cord injury by transplantation of bone marrow mesenchymal-stem cell-derived neurons. Chin Med J (Engl) 2005; 118: 1533–1541.

    CAS  Google Scholar 

  89. Lu P, Jones LL, Tuszynski MH . BDNF-expressing marrow stromal cells support extensive axonal growth at sites of spinal cord injury. Exp Neurol 2005; 191: 344–360.

    Article  CAS  PubMed  Google Scholar 

  90. Basso DM, Beattie MS, Bresnahan JC . A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 1995; 12: 1–21.

    Article  CAS  PubMed  Google Scholar 

  91. King VR, Phillips JB, Hunt-Grubbe H, Brown R, Priestley JV . Characterization of non-neuronal elements within fibronectin mats implanted into the damaged adult rat spinal cord. Biomaterials 2006; 27: 485–496.

    Article  CAS  PubMed  Google Scholar 

  92. Mansilla E, Marin GH, Sturla F, Drago HE, Gil MA, Salas E et al. Human mesenchymal stem cells are tolerized by mice and improve skin and spinal cord injuries. Transplant Proc 2005; 37: 292–294.

    Article  CAS  PubMed  Google Scholar 

  93. Sykova E, Jendelova P, Urdzikova L, Lesny P, Hejcl A . Bone marrow stem cells and polymer hydrogels – two strategies for spinal cord injury repair. Cell Mol Neurobiol 2006; 26: 1113–1129.

    Article  CAS  PubMed  Google Scholar 

  94. Himes BT, Neuhuber B, Coleman C, Kushner R, Swanger SA, Kopen GC et al. Recovery of function following grafting of human bone marrow-derived stromal cells into the injured spinal cord. Neurorehabil Neural Repair 2006; 20: 278–296.

    Article  PubMed  Google Scholar 

  95. Park HC, Shim YS, Ha Y, Yoon SH, Park SR, Choi BH 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: 913–922.

    Article  CAS  PubMed  Google Scholar 

  96. Neuhuber B, Timothy Himes B, Shumsky JS, Gallo G, Fischer I . Axon growth and recovery of function supported by human bone marrow stromal cells in the injured spinal cord exhibit donor variations. Brain Res 2005; 1035: 73–85.

    Article  CAS  PubMed  Google Scholar 

  97. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8: 315–317.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

A Keating holds the Gloria and Seymour Epstein Chair in Cell Therapy and Transplantation at University Health Network and the University of Toronto. A Parr is funded by the Canadian Institutes of Health Research and the University of Toronto.

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Parr, A., Tator, C. & Keating, A. Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury. Bone Marrow Transplant 40, 609–619 (2007). https://doi.org/10.1038/sj.bmt.1705757

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