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Indian Journal of Neurotrauma 2014; 11(01): 30-38
DOI: 10.1016/j.ijnt.2014.05.008
Review Article
Thieme Medical and Scientific Publishers Private Ltd.

Stem cell treatment for the spinal cord injury – A concise review

Venkatesh Ponemone
a   TotipotentRX Centre for Cellular Medicine, Fortis Memorial Research Institute, Gurgaon 122002, NCR Delhi, India
,
Khushboo Choudhury
a   TotipotentRX Centre for Cellular Medicine, Fortis Memorial Research Institute, Gurgaon 122002, NCR Delhi, India
,
Kenneth Lee Harris
a   TotipotentRX Centre for Cellular Medicine, Fortis Memorial Research Institute, Gurgaon 122002, NCR Delhi, India
,
Yashbir Dewan
b   Max Institute of Neurosciences, Dehradun, Uttarakhand, India
› Author Affiliations
Subject Editor:
Further Information

Publication History

19 May 2014

28 May 2014

Publication Date:
06 April 2017 (online)

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Abstract

A spinal cord injury (SCI) is any injury of the spinal cord caused due to trauma and mostly comprise of damage to the nerves associated with the spinal cord and they can be classified as being complete or incomplete. Spinal cord injuries account for a majority of lower body disabilities due to accidents and trauma. Cell transplantation, as a therapeutic intervention for spinal cord injury (SCI), has been extensively studied by scientists and researchers in recent years using stem cell that has shown considerable promise in treating patients with SCI and thus restores lost functions by replacing lost or damaged cell populations. Spinal cord injuries account for a majority of lower body disabilities due to accidents and trauma. SCI also paves way for a lot of other disabilities associated with blood vessels as well and bone deformities. The global burden of SCI, economically, runs into millions as complete cure is not possible. The number of clinical trials that have been conducted for phase 1 studies of spinal cord injury is a staggering number and currently 246 trials are being conducted in their initial phases. However, many questions remain unanswered and more continue to emerge. This review will comprehensively cover publications in the field from the last years and examine the biological effects of SCI.

Keywords

Spinal cord injury - Stem cells - Bone marrow - Bone marrow derived stem cells - Mesenchymal stem cells
 

  • References

  • 1 Sekhon L.H., Fehlings M.G.. Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine 2001; 26 (24) 2-12
    CrossrefPubMedGoogle Scholar
  • 2 Christopher and Dana Reeve Foundation. One Degree of Separation: Paralysis and SpinalCordInjury inthe United States. 2010.
    PubMed
  • 3 Spinal Cord Injury Facts and Figures at a Glance. Birmingham, Alabama: National Spinal Cord Injury Statistical Center; 2010.
    PubMed
  • 4 Young W.. Spinal cord contusion models. Prog Brain Res 2002; 231-255 [Chapter 17]
    PubMedGoogle Scholar
  • 5 Popovich P.G., Guan Z., McGaughy V., Fisher L., Hickey W.F., Basso D.M.. The neuropathological, behavioural consequences of intraspinal microglial/macrophage activation. J Neuropathol Exp Neurol 2002; 61: 623-633
    CrossrefPubMedGoogle Scholar
  • 6 Carlson S.L.. Acute inflammatory response in the spinal cord following impact injury. Exp Neurol 1999; 151: 77-88
    PubMedGoogle Scholar
  • 7 McKerracher L., David S., Jackson D.L.. et al Identification of myelin associated glycoprotein as a major myelin-derived inhibitor of neurite outgrowth. Neuron 1994; 13: 805-811
    CrossrefPubMedGoogle Scholar
  • 8 Figley S.A., Austin J.W., Rowland J.W., Fehlings M.G.. Pathophysiology of Spinal Cord Injury, in The Cervical Spine. 2011. Lippincott, Williams and Wilkins; Philadelphia: [in review]
    Google Scholar
  • 9 Benzel E.C.. Management of acute spinal cord injury. In: Wilkins R.H., Rengachary S.S.. eds. Neurosurgery. 1996. Williams & Wilkins; Philadelphia: 2861-2866
    Google Scholar
  • 10 Bai L., Lennon D.P., Eaton V.. et al Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis. Glia 2009; 57: 1192-1203
    CrossrefPubMedGoogle Scholar
  • 11 Bottai D., Cigognini D., Madaschi L.. et al Embryonic stem cells promote motor recovery and affect inflammatory cell infiltration in spinal cord injured. Exp Neurol 2010; 223 (02) 452-463
    CrossrefPubMedGoogle Scholar
  • 12 Jaderstad J., Jaderstad L.M., Li J.. et al Communication via gap junctions underlies early functional and beneficial interactions between grafted neural stem cells and the host. Proc Natl Acad Sci 2010; 107: 5184-5190
    CrossrefPubMedGoogle Scholar
  • 13 Arriola A., Kiel M.E., Shi Y., McKinnon R.D.. Adjunctive MSCs enhance myelin formation by xenogenic oligodendrocyte precursors transplanted in the retina. Cell Res 2010; 20: 728-731
    CrossrefPubMedGoogle Scholar
  • 14 Tetzlaff W., Okon E.B., Karimi-Abdolrezaee S.. et al A systematic review of cellular transplantation therapies for spinal cord injury. J Neurotrauma 2011; 28: 1611-1682
    CrossrefPubMedGoogle Scholar
  • 15 Campagnoli C., Roberts I.A., Kumar S., Bennett P.R., Bellantuono I., Fisk N.M.. Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood 2001; 98: 2396-2402
    CrossrefPubMedGoogle Scholar
  • 16 Chen M.S., Huber A.B., van der Haar M.E.. et al Nogo-A is a myelin associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 2000; 403: 434-439
    CrossrefPubMedGoogle Scholar
  • 17 Karimi-Abdolrezaee S., Eftekharpour E., Wang J., Schut D., Fehlings M.G.. Synergistic effects of transplanted adult neural stem/progenitor cells, chondroitinase, and growth factors promote functional repair and plasticity of the chronically injured spinal cord. J Neurosci 2010; 30: 1657-1676
    CrossrefPubMedGoogle Scholar
  • 18 Sasaki M., Honmou O., Akiyama Y., Uede T., Hashi K., Koscis J.D.. Transplantation of an acutely isolated bone marrow fraction repairs demyelinated adult rat spinal cord axons. Glia 2001; 35: 26-34
    CrossrefPubMedGoogle Scholar
  • 19 Akiyama Y., Radtke C., Honmou S., Koscis J.D.. Remyelination of the spinal cord following intravenous delivery of bone marrow stromal cells. Glia 2002; 39: 229-236
    CrossrefPubMedGoogle Scholar
  • 20 Akiyama Y., Radtke C., Kocsis J.D.. Remyelination of the rat spinal cord by transplantation of identified bone marrow stromal cells. J Neurosci 2002; 22: 6623-6630
    PubMedGoogle Scholar
  • 21 Wu S., Suzuki Y., Ejiri Y.. et al Bone marrow stromal cells enhance differentiation of co-cultured neurosphere cells and promote regeneration of the injured spinal cord. J Neurosci Res 2003; 72: 343-351
    CrossrefPubMedGoogle Scholar
  • 22 Wilson A., Trump A.. Bone-marrow haematopoietic stem-cell niches (review). Nat Rev Immunol 2006; 06: 93-105
    CrossrefPubMedGoogle Scholar
  • 23 Pittenger M.F., Mackay A., Beck S.C.. et al Multilineage potential of adult mesenchymal stem cells. Science 1999; 284: 145-147
    PubMedGoogle Scholar
  • 24 Takakura N., Watanabe T., Suenobu S.. et al A role for hematopoietic stem cells in promoting angiogenesis. Cell 2000; 102: 199-209
    CrossrefPubMedGoogle Scholar
  • 25 Ikegami T., Nakamura M., Yamane J.. et al Chondroitinase ABC combined with neural stem/progenitor cell transplantation enhances graft cell migration and outgrowth of growth-associated protein-43-positive fibers after rat spinal cord injury. Eur J Neurosci 2005; 22: 3036-3046
    CrossrefPubMedGoogle Scholar
  • 26 Neuhuber B., Himes B.T., Shumsky J.S., 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
    CrossrefPubMedGoogle Scholar
  • 27 Hofstetter C.P., Schwarz E., Hess D.. et al Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc Natl Acad Sci USA 2002; 99 (04) 2199-2204
    CrossrefPubMedGoogle Scholar
  • 28 Wislet-Gendebien S., Hans G., Leprince P., Rigo J.M., Moonen G., Rogister B.. Plasticity of cultured mesenchymal stem cells: switch from nestin-positive to excitable neuron-like phenotype. Stem Cells 2005; 23: 392-402
    CrossrefPubMedGoogle Scholar
  • 29 Crigler L., Robey R.C., Asawachaicharn A., Gaupp D., Phinney D.G.. Human mesenchymal stem cell subpopulations express a variety of neuro-regulatory molecules and promote neuronal cell survival and neuritogenesis. Exp Neurol 2006; 198: 54-64
    CrossrefPubMedGoogle Scholar
  • 30 Martens D.J., Seaberg R.M., van der Kooy D.. In vivo infusions of exogenous growth factors into the fourth ventricle of the adult mouse brain increase the proliferation of neural progenitors around the fourth ventricle and the central canal of the spinal cord. Eur J Neurosci 2002; 16: 1045-1057
    CrossrefPubMedGoogle Scholar
  • 31 Cao Q.L., Zhang Y.P., Howard R.M.. Pluripotent stem cells engrafted into the normal or lesioned adult rat spinal cord is restricted to a glial lineage. Exp Neurol 2001; 167: 48-58
    CrossrefPubMedGoogle Scholar
  • 32 Ogawa Y., Sawamoto K., Miyata T.. Transplantation of in vitro-expanded fetal neural progenitor cells results in neurogenesis and functional recovery after spinal cord contusion injury in adult rats. J Neurosci Res 2002; 69: 925-933
    CrossrefPubMedGoogle Scholar
  • 33 Iwanami A., Kaneko S., Nakamura M.. et al Transplantation of human neural stem cells for spinal cord injury in primates. J Neurosci Res 2005; 80: 182-190
    CrossrefPubMedGoogle Scholar
  • 34 Park H.S., Shim Y.S., Ha Y.. 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
    CrossrefPubMedGoogle Scholar
  • 35 Raineteau O., Schwab M.E.. Plasticity of motor neurons after incomplete spinal cord injury. Nat Rev Neurosci 2001; 02 (04) 263-273
    CrossrefPubMedGoogle Scholar
  • 36 Ramer L.M., Ramer M.S., Steeves J.D.. Setting the stage for functional repair of spinal cord injuries: a cast of thousands. Spinal Cord 2005; 43 (03) 134-161
    CrossrefPubMedGoogle Scholar
  • 37 Dietz V.G., Heiner S.. Cell Memorial Lecture: neuronal plasticity after spinal cord injury: Significance for present and future treatments. J Spinal Cord Med 2006; 29 (05) 481-488
    PubMedGoogle Scholar
  • 38 Li Y., Field P.M., Raisman G.. Regeneration of adult rat corticospinal axons induced by transplanted olfactory ensheathing cells. J Neurosci 1998; 08 (24) 10514-10524
    PubMedGoogle Scholar
  • 39 Keyvan-Fouladi N., Raisman G., Li Y.. Functional repair of the corticospinal tract by delayed transplantation of olfactory ensheathing in adult rats. J Neurosci 2003; 23: 9428-9434
    PubMedGoogle Scholar
  • 40 Barnett S.C., Chang L.. Olfactory ensheathing cells and CNS repair: going solo or in need of a friend?. Trends Neurosci 2004; 27: 54-60
    CrossrefPubMedGoogle Scholar
  • 41 Ramon-Cueto A., Cordero M.I., Santos-Benito F.F., Avila J.. Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia. Neuron 2000; 25: 425-453
    CrossrefPubMedGoogle Scholar
  • 42 Polentes J., Stamegna J.C., Nieto-Sampedro M., Gauthier P.. Phrenic rehabilitation and diaphragm recovery after cervical injury and transplantation of olfactory ensheathing cells. Neurobiol Dis 2004; 16: 638-653
    CrossrefPubMedGoogle Scholar
  • 43 Lu J., Feron F., Ho S.M., Mackay-Sim A., Waite P.M.. Transplantation of nasal olfactory tissue promotes partial recovery in paraplegic adult rats. Brain Res 2001; 889: 344-357
    CrossrefPubMedGoogle Scholar
  • 44 Radtke C., Akiyama Y., Brokaw J.. et al Remyelination of the nonhuman primate spinal cord by transplantation of H-transferase transgenic adult pig olfactory ensheathing cells. Faseb J 2004; 18: 335-337
    PubMedGoogle Scholar
  • 45 Jendelova P., Herynek V., Urdzikova L.. et al Magnetic resonance tracking of transplanted bone marrow and embryonic stem cells labeled by iron oxide nanoparticles in rat brain and spinal cord. J Neurosci Res 2004; 76 (02) 232-243
    CrossrefPubMedGoogle Scholar
  • 46 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; 08 (04) 668-676
    CrossrefPubMedGoogle Scholar
  • 47 Kumagai G., Okada Y., Yamane J.. et al Roles of ES-cell derived gliogenic neural stem/progenitor cells in functional recovery after spinal cord injury. PLoS ONE 2009; 04 (11) 7706
    CrossrefPubMedGoogle Scholar
  • 48 Lowry N., Goderie S.K., Adamo M.. et al Multipotent embryonic spinal cord stem cells expanded by endothelial factors and Shh/RA promote functional recovery after spinal cord injury. Experi Neurol 2008; 209: 510-522
    PubMedGoogle Scholar
  • 49 Falk A., Koch P., Kesavan J.. et al Capture of neuroepithelial like stem cells provides a versatile system for in vitro production of human neurons. PLoS ONE 2012; 07 (01) e29597
    CrossrefPubMedGoogle Scholar
  • 50 Massey J.M., Amps J., Viapiano M.S.. et al Increased chondroitin sulfate proteoglycan expression in denervated brainstem targets following spinal cord injury creates a barrier to axonal regeneration overcome by chondroitinase ABC and neurotrophin. Exp Neurol 2008; 209: 426-445
    CrossrefPubMedGoogle Scholar
  • 51 Zhang H.T., Cheng H.Y., Cai Y.Q.. et al Comparison of adult neurospheres derived from different origins for treatment of rat spinal cord injury. Neurosci Lett 2009; 458: 16-21
    PubMedGoogle Scholar
  • 52 Fawcett J.W., Curt A., Steeves J.D.. et al Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials. Spinal Cord 2007; 45: 190-205
    CrossrefPubMedGoogle Scholar
  • 53 Syková E., Homola A., Mazanec R.. et al Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury. Cell Transpl 2006; 15: 675-687
    CrossrefPubMedGoogle Scholar
  • 54 Reynolds B.A., Weiss S.. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 1992; 255: 1707-1710
    CrossrefPubMedGoogle Scholar
  • 55 Lu P., Jones L.L., Tuszynski M.H.. BDNF-expressing marrow stromal cells support extensive axonal growth at sites of spinal cord injury. Exp Neurol 2005; 191: 344-360
    CrossrefPubMedGoogle Scholar
  • 56 Sigurjonsson O.E., Perreault M.C., Egeland T., Glover J.C.. Adult human hematopoietic stem cells produce neurons efficiently in the regenerating chicken embryo spinal cord. Proc Nat Acad Sci USA 2005; 102: 5227-5232
    CrossrefPubMedGoogle Scholar
  • 57 Čĩzková D., Rosocha J., Vanicky I., Jergova S., Cizek M.. Transplantation of human mesenchymal stem cells improve functional recovery after spinal cord injury in the rat. Cell Mol Neurobiol 2006; 26: 1167-1180
    PubMedGoogle Scholar
  • 58 Himes B.T., Neuhuber B., Coleman C.. et al Recovery of function following grafting of human bone marrow-derived stromal cells into the injured spinal cord. Neurorehabil Neural Repair 2008; 20: 278-296
    PubMedGoogle Scholar
  • 59 Courtney P., Samdani A.F., Betz R.R.. Grafting of human bone marrow stromal cells into spinal cord injury: a comparison of delivery methods. Spine 2009; 34: 328-334
    CrossrefPubMedGoogle Scholar
  • 60 Samdani A.F., Paul C., Betz R.R., Fischer I., Neuhuber B.. Transplantation of human marrow stromal cells and mono-nuclear bone marrow cells into the injured spinal cord. Spine 2009; 34: 2605-2612
    CrossrefPubMedGoogle Scholar
  • 61 Yoon S.H., Shim Y.S., Park Y.H.. et al Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor: phase I/II clinical train. Stem Cells 2007; 25: 2066-2073
    CrossrefPubMedGoogle Scholar
  • 62 Pal R., Venkataramana N.K., Bansal A.. et al Ex vivo-expanded autologous bone marrow-derived mesenchymal stromal cells in human spinal cord injury/paraplegia: a pilot clinical study. Cytotherapy 2009; 11: 897-911
    CrossrefPubMedGoogle Scholar
  • 63 Deda H., Inci M., Kurecki A.. et al Treatment of chronic spinal cord injured patients with autologous bone marrow-derived hematopoietic stem cell transplantation: 1-year follow-up. Cytotherapy 2008; 10: 565-574
    CrossrefPubMedGoogle Scholar
  • 64 Nothias J.M., Mitsui T., Shumsky J.S., Fischer I., Antonacci M.D., Murray M.. Combined effects of neurotrophin secreting transplants, exercise, and serotonergic drug challenge improve function in spinal rats. Neurorehabil Neural Repair 2005; 19: 296-312
    CrossrefPubMedGoogle Scholar
  • 65 Callera F.. do Nascimento. Delivery of autologous bone marrow precursor cells into the spinal cord via lumbar puncture technique in patients with spinal cord injury: a preliminary safety study. Exp Hematol 2006; 34: 130-131
    CrossrefPubMedGoogle Scholar
  • 66 Wernig M., Zhao J.P., Pruszak J.. 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 USA 2008; 105: 5856-5861
    CrossrefPubMedGoogle Scholar
  • 67 Geffner L.F., Santacruz P., Izurieta M.. et al Administration of autologous bone marrow stem cells into spinal cord injury patients via multiple routes is safe and improves their quality of life: comprehensive case studies. Cell 2008; 17 (05) 1277-1293
    PubMedGoogle Scholar
  • 68 Yamanaka S.. A fresh look at iPS cells. Cell 2009; 137: 13-17
    CrossrefPubMedGoogle Scholar