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Journal of Neurorestoratology 2014, 2(1): 15-24 https://doi.org/10.2147/JN.S49208
Review | Open Access | Issue | Published: 05 December 2013

Review of recently documented clinical neuroprotective and cellular treatment for spinal cord injury: an analysis of outcomes

Show Author's Information Hooshang Saberi1,2( ),  Nazi Derakhshanrad1,  Mir Saeed Yekaninejad1,3
Brain and Spinal Injuries Research Center,
Department of Neurosurgery, Imam Khomeini Hospital,
Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
Keywords:
cell transplantation, spinal cord injury, neuroprotective treatment
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Saberi H, Derakhshanrad N, Yekaninejad MS. Review of recently documented clinical neuroprotective and cellular treatment for spinal cord injury: an analysis of outcomes. Journal of Neurorestoratology, 2014, 2(1): 15-24. https://doi.org/10.2147/JN.S49208
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Abstract Full text About this article

Emergence of new neuroprotective treatments for spinal cord injury (SCI) in recent clinical studies is a matter of great scientific and public interest. Effect size and complication rates are of particular concern. In this study, a search was performed in the PubMed, Scopus, and Scholar Google search engines using the keywords "spinal cord injury", "cell transplantation" and "neuroprotective". Clinical studies published in the English language were included. Using the study inclusion criteria, 45 clinically relevant studies were found in which neurologic changes was descriptively reported. Of these, 20 studies with American Spinal Injury Association scale, and sensory and motor reports were included for quantitative review. Overall, these papers show an increment in the number of studies reported since the turn of the century, and recent endeavors in the field have accelerated. To compare newer and older studies, considering sufficient numbers of studies in each group, the year 2010 was identified as the turning point. The mean ± standard deviation change in motor score after treatment was 8.67±3.48 in reports before 2010, and this increased to 8.95±2.78 after 2010. Similarly, the mean change in score for light touch was 9.57±3.63 before 2010 and increased to 10.58±3.06 after 2010. The mean change in score for pinprick sensation improved from 8.36±2.82 before 2010 to 8.39±2.69 after 2010. Our study indicates that cellular and neuroprotective therapies are becoming more popular, and the mean neurologic effect size in terms of light touch shows an increment, paving the pathway for clinical applications to be established in the near future.


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About this article

Review of recently documented clinical neuroprotective and cellular treatment for spinal cord injury: an analysis of outcomes

Show Author's information Hooshang Saberi1,2( ), Nazi Derakhshanrad1, Mir Saeed Yekaninejad1,3
Brain and Spinal Injuries Research Center,
Department of Neurosurgery, Imam Khomeini Hospital,
Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Emergence of new neuroprotective treatments for spinal cord injury (SCI) in recent clinical studies is a matter of great scientific and public interest. Effect size and complication rates are of particular concern. In this study, a search was performed in the PubMed, Scopus, and Scholar Google search engines using the keywords "spinal cord injury", "cell transplantation" and "neuroprotective". Clinical studies published in the English language were included. Using the study inclusion criteria, 45 clinically relevant studies were found in which neurologic changes was descriptively reported. Of these, 20 studies with American Spinal Injury Association scale, and sensory and motor reports were included for quantitative review. Overall, these papers show an increment in the number of studies reported since the turn of the century, and recent endeavors in the field have accelerated. To compare newer and older studies, considering sufficient numbers of studies in each group, the year 2010 was identified as the turning point. The mean ± standard deviation change in motor score after treatment was 8.67±3.48 in reports before 2010, and this increased to 8.95±2.78 after 2010. Similarly, the mean change in score for light touch was 9.57±3.63 before 2010 and increased to 10.58±3.06 after 2010. The mean change in score for pinprick sensation improved from 8.36±2.82 before 2010 to 8.39±2.69 after 2010. Our study indicates that cellular and neuroprotective therapies are becoming more popular, and the mean neurologic effect size in terms of light touch shows an increment, paving the pathway for clinical applications to be established in the near future.

Keywords: cell transplantation, spinal cord injury, neuroprotective treatment

References(58)

1.
Aidinoff E, Front L, Itzkovich M, et al. Expected spinal cord independence measure, third version, scores for various neurological levels after complete spinal cord lesions. Spinal Cord. 2011;49(8):893–896.
DOI Google Scholar
2.
Harrop JS, Hashimoto R, Norvell D, et al. Evaluation of clinical experience using cell-based therapies in patients with spinal cord injury: a systematic review. J Neurosurg Spine. 2012;17(Suppl 1):230–246.
DOI Google Scholar
3.
Kramer AS, Harvey AR, Plant GW, Hodgetts SI. Systematic review of induced pluripotent stem cell technology as a potential clinical therapy for spinal cord injury. Cell Transplant. 2013;22(4):571–617.
DOI Google Scholar
4.
Firouzi M, Moshayedi P, Saberi H, et al. Transplantation of Schwann cells to subarachnoid space induces repair in contused rat spinal cord. Neurosci Lett. 2006;402(1–2):66–70.
DOI Google Scholar
5.
Fehlings MG, Vawda R. Cellular treatments for spinal cord injury: the time is right for clinical trials. Neurotherapeutics. 2011;8(4):704–720.
DOI Google Scholar
6.
Fawcett JW, Curt A, Steeves JD, 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(3):190–205.
DOI Google Scholar
7.
Lammertse D, Tuszynski MH, Steeves JD, et al. Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: clinical trial design. Spinal Cord. 2007;45(3):232–242.
DOI Google Scholar
8.
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):206–221.
DOI Google Scholar
9.
Tuszynski MH, Steeves JD, Fawcett JW, et al. Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: clinical trial inclusion/exclusion criteria and ethics. Spinal Cord. 2007;45(3):222–231.
DOI Google Scholar
10.
Abdelaziz OS, Marie A, Abbas M, Ibrahim M, Gabr H. Feasibility, safety, and efficacy of directly transplanting autologous adult bone marrow stem cells in patients with chronic traumatic dorsal cord injury: a pilot clinical study. Neurosurg Q. 2010;20(3):216–226.
DOI Google Scholar
11.
Adel N, Gabr H, Hamdy S, Afifi L, Mahmoud H. Stem cell therapy in chronic spinal cord injuries. Egyptian Journal of Neurology, Psychiatry and Neurosurgery. 2009;46(2):467–478.
Google Scholar
12.
Bhanot Y, Rao S, Ghosh D, Balaraju S, Radhika CR, Satish Kumar KV. Autologous mesenchymal stem cells in chronic spinal cord injury. Br J Neurosurg. 2011;25(4):516–522.
DOI Google Scholar
13.
Callera F, de Melo CM. Magnetic resonance tracking of magnetically labeled autologous bone marrow CD34+ cells transplanted into the spinal cord via lumbar puncture technique in patients with chronic spinal cord injury: CD34+ cells’ migration into the injured site. Stem Cells Dev. 2007;16(3):461–466.
DOI Google Scholar
14.
Chhabra HS, Lima C, Sachdeva S, et al. Autologous olfactory [corrected] mucosal transplant in chronic spinal cord injury: an Indian pilot study. Spinal Cord. 2009;47(12):887–895.
DOI Google Scholar
15.
Kumar AA, Kumar SR, Narayanan R, Arul K, Baskaran M. Autologous bone marrow derived mononuclear cell therapy for spinal cord injury: a phase I/II clinical safety and primary efficacy data. Exp Clin Transplant. 2009;7(4):241–248.
Google Scholar
16.
Pal R, Venkataramana NK, 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(7):897–911.
DOI Google Scholar
17.
Mehta T, Feroz A, Thakkar U, Vanikar A, Shah V, Trivedi H. Subarachnoid placement of stem cells in neurological disorders. Transplant Proc. 2008;40(4):1145–1147.
DOI Google Scholar
18.
Lima C, Escada P, Pratas-Vital J, et al. Olfactory mucosal autografts and rehabilitation for chronic traumatic spinal cord injury. Neurorehabil Neural Repair. 2009;24(1):10–22.
DOI Google Scholar
19.
Cristante AF, Barros-Filho TE, Tatsui N, et al. Stem cells in the treatment of chronic spinal cord injury: evaluation of somatosensitive evoked potentials in 39 patients. Spinal Cord. 2009;47(10):733–738.
DOI Google Scholar
20.
Mackay-Sim A, Feron F, Cochrane J, et al. Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial. Brain. 2008;131(Pt 9):2376–2386.
DOI Google Scholar
21.
Pitts LH, Ross A, Chase GA, Faden AI. Treatment with thyrotropin-releasing hormone (TRH) in patients with traumatic spinal cord injuries. J Neurotrauma. 1995;12(3):235–243.
DOI Google Scholar
22.
Geisler FH, Dorsey FC, Coleman WP. Recovery of motor function after spinal-cord injury – a randomized, placebo-controlled trial with GM-1 ganglioside. N Engl J Med. 1991;324(26):1829–1838.
DOI Google Scholar
23.
Guest J, Herrera LP, Qian T. Rapid recovery of segmental neurological function in a tetraplegic patient following transplantation of fetal olfactory bulb-derived cells. Spinal Cord. 2006;44(3):135–142.
DOI Google Scholar
24.
Geffner LF, 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 Transplant. 2008;17(12):1277–1293.
DOI Google Scholar
25.
Ra JC, Shin IS, Kim SH, et al. Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. Stem Cells Dev. 2011;20(8):1297–1308.
DOI Google Scholar
26.
Kang KS, Kim SW, Oh YH, et al. A 37-year-old spinal cord-injured female patient, transplanted of multipotent stem cells from human UC blood, with improved sensory perception and mobility, both functionally and morphologically: a case study. Cytotherapy. 2005;7(4):368–373.
DOI Google Scholar
27.
Yoon SH, Shim YS, Park YH, 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 trial. Stem Cells. 2007;25(8):2066–2073.
DOI Google Scholar
28.
Park HC, Shim YS, 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(5–6):913–922.
DOI Google Scholar
29.
Park JH, Kim DY, Sung IY, et al. Long-term results of spinal cord injury therapy using mesenchymal stem cells derived from bone marrow in humans. Neurosurgery. 2011;70(5):1238–1247.
DOI Google Scholar
30.
Moviglia GA, Fernandez Vina R, Brizuela JA, et al. Combined protocol of cell therapy for chronic spinal cord injury. Report on the electrical and functional recovery of two patients. Cytotherapy. 2006;8(3):202–209.
DOI Google Scholar
31.
Moviglia GA, Varela G, Brizuela JA, et al. Case report on the clinical results of a combined cellular therapy for chronic spinal cord injured patients. Spinal Cord. 2009;47(6):499–503.
DOI Google Scholar
32.
Deda H, Inci MC, Kurekci AE, 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(6):565–574.
DOI Google Scholar
33.
Frolov AA, Bryukhovetskiy AS. Effects of haematopoietic autologous stem cell transplantation to the chronically injured human spinal cord evaluated by motor and somatosensory evoked potentials methods. Cell Transplant. 2012;21 Suppl 1:S49–S55.
DOI Google Scholar
34.
Rabinovich SS, Seledtsov VI, Poveschenko OV, et al. Transplantation treatment of spinal cord injury patients. Biomed Pharmacother. 2003;57(9):428–433.
DOI Google Scholar
35.
Chernykh ER, Stupak VV, Muradov GM, et al. Application of autologous bone marrow stem cells in the therapy of spinal cord injury patients. Bull Exp Biol Med. 2007;143(4):543–547.
DOI Google Scholar
36.
Seledtsova GV, Rabinovich SS, Belogorodtsev SN, Parlyuk OV, Seledtsov VI, Kozlov VA. Delayed results of transplantation of fetal neurogenic tissue in patients with consequences of spinal cord trauma. Bull Exp Biol Med. 2011;149(4):530–533.
DOI Google Scholar
37.
Fehlings MG, Theodore N, Harrop J, et al. A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury. J Neurotrauma. 2011;28(5):787–796.
DOI Google Scholar
38.
Falci S, Holtz A, Akesson E, et al. Obliteration of a posttraumatic spinal cord cyst with solid human embryonic spinal cord grafts: first clinical attempt. J Neurotrauma. 1997;14(11):875–884.
DOI Google Scholar
39.
Huang H, Xi H, Chen L, Zhang F, Liu Y. Long-term outcome of olfactory ensheathing cell therapy for patients with complete chronic spinal cord injury. Cell Transplant. 2012;21 Suppl 1:S23–S31.
DOI Google Scholar
40.
Zhou XH, Ning GZ, Feng SQ, et al. Transplantation of autologous activated Schwann cells in the treatment of spinal cord injury: six cases, more than five years of follow-up. Cell Transplant. 2012;21 Suppl 1:S39–S47.
DOI Google Scholar
41.
Wu J, Sun T, Ye C, Yao J, Zhu B, He H. Clinical observation of fetal olfactory ensheathing glia transplantation (OEGT) in patients with complete chronic spinal cord injury. Cell Transplant. 2012;21 Suppl 1:S33–S37.
DOI Google Scholar
42.
Saberi H, Firouzi M, Habibi Z, et al. Safety of intramedullary Schwann cell transplantation for postrehabilitation spinal cord injuries: 2-year follow-up of 33 cases. J Neurosurg Spine. 2011;15(5):515–525.
DOI Google Scholar
43.
Karamouzian S, Nematollahi-Mahani SN, Nakhaee N, Eskandary H. Clinical safety and primary efficacy of bone marrow mesenchymal cell transplantation in subacute spinal cord injured patients. Clin Neurol Neurosurg. 2012;114(7):935–939.
DOI Google Scholar
44.
Saito F, Nakatani T, Iwase M, et al. Spinal cord injury treatment with intrathecal autologous bone marrow stromal cell transplantation: the first clinical trial case report. J Trauma. 2008;64(1):53–59.
DOI Google Scholar
45.
Saito F, Nakatani T, Iwase M, et al. Administration of cultured autologous bone marrow stromal cells into cerebrospinal fluid in spinal injury patients: a pilot study. Restor Neurol Neurosci. 2012;30(2):127–136.
DOI Google Scholar
46.
Sakuma T, Yamazaki M, Okawa A, et al. Neuroprotective therapy using granulocyte colony-stimulating factor for patients with worsening symptoms of compression myelopathy, Part 1: a phase I and IIa clinical trial. Eur Spine J. 2012;21(3):482–489.
DOI Google Scholar
47.
Sakuma T, Yamazaki M, Okawa A, et al. Neuroprotective therapy using granulocyte colony-stimulating factor for patients with worsening symptoms of thoracic myelopathy: a multicenter prospective controlled trial. Spine (Phila Pa 1976). 2012;37(17):1475–1478.
DOI Google Scholar
48.
Takahashi H, Yamazaki M, Okawa A, et al. Neuroprotective therapy using granulocyte colony-stimulating factor for acute spinal cord injury: a phase I/IIa clinical trial. Eur Spine J. 2012;21(12):2580–2587.
DOI Google Scholar
49.
Kishk NA, Gabr H, Hamdy S, et al. Case control series of intrathecal autologous bone marrow mesenchymal stem cell therapy for chronic spinal cord injury. Neurorehabil Neural Repair. 2010;24(8):702–708.
DOI Google Scholar
50.
Cheng H, Liao KK, Liao SF, Chuang TY, Shih YH. Spinal cord repair with acidic fibroblast growth factor as a treatment for a patient with chronic paraplegia. Spine (Phila Pa 1976). 2004;29(14):E284–E288.
DOI Google Scholar
51.
Knoller N, Auerbach G, Fulga V, et al. Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: phase I study results. J Neurosurg Spine. 2005;3(3):173–181.
DOI Google Scholar
52.
Sykova E, Homola A, Mazanec R, et al. Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury. Cell Transplant. 2006;15(8–9):675–687.
DOI Google Scholar
53.
Hammadi AA, Marino A, Farhan S. Clinical response of 277 patients with spinal cord injury to stem cell therapy in Iraq. Int J Stem Cells. 2012;5(1):76–78.
DOI Google Scholar
54.
Kato K, Yamazaki M, Okawa A, et al. Intravenous administration of granulocyte colony-stimulating factor for treating neuropathic pain associated with compression myelopathy: a phase I and IIa clinical trial. Eur Spine J. 2012;22(1):197–204.
DOI Google Scholar
55.
Mackay-Sim A, St John JA. Olfactory ensheathing cells from the nose: clinical application in human spinal cord injuries. Exp Neurol. 2010;229(1):174–180.
DOI Google Scholar
56.
Saberi H, Moshayedi P, Aghayan HR, et al. Treatment of chronic thoracic spinal cord injury patients with autologous Schwann cell transplantation: an interim report on safety considerations and possible outcomes. Neurosci Lett. 2008;443(1):46–50.
DOI Google Scholar
57.
Rad ND, Saberi H, Yekaninejad MS, et al. Safety of granulocyte-colony stimulating factor (G-CSF) administration for post rehabilitated motor complete spinal cord injury patients: an open label, phase one study. Cell Transplant. August 29, 2013. [Epub ahead of print.]
Google Scholar
58.
Guest J, Harrop JS, Aarabi B, et al. Optimization of the decision-making process for the selection of therapeutics to undergo clinical testing for spinal cord injury in the North American Clinical Trials Network. J Neurosurg Spine. 2012;17(Suppl 1):94–101.
DOI Google Scholar
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Publication history

Published: 05 December 2013
Issue date: December 2014

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© 2014 The Author(s).

Acknowledgements

The authors are grateful to the researchers who have published their work, thereby providing the material for this study. We also thank Rasoul Mansouri for preparing the international geographic plot of the studies.

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