Cell Therapy and Gene Therapy in Spinal Cord Injuries

Document Type : Review Article

Author

PhD in Molecular Genetics, Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

Abstract

Stem cells are counts as a promising tool for treating spinal cord injury (SCI), due to their high proliferation and self-renewal capacities. Many advances in the field of gene therapy and in particular cell therapy of SCI have been made at three levels of experimental, pre-clinical, and clinical practice, owing to the multiple capabilities of stem cells. But, in order to find a therapeutic approach to ultimately reach the clinical level, a number of barriers, such as ethical, tumorigenicity, immune rejection, differentiation to non-intended cells, and clinical-trial-associated problems must be resolved. Many strategies for optimization of the route, location, and time of cell administration have also been developed in this field. Literature reveals that mesenchymal stem cells (MSCs) have the most prominent benefit for clinical applications, compared with other types of stem cells. However, it appears that the recent method of in-vitro trans-differentiation of somatic cells has the potential to substitute the current beneficial MSC transplantation method, in the near future. According to the complex pathophysiology of SCI, the combination therapies (that is simultaneous application of different treatment approaches such as cell therapy, gene therapy, simultaneous application of several types of cells in combination with nanomaterial scaffolds, and ...) are considered to be more useful in SCI treatments rather than single therapies. Finally, it should be noted that due to the safety problems attributed to cell and gene therapy application, patients are not recommended to participate in experimental treatments other than formal clinical trials.

Keywords

References

  1. Oh SK, Jeon SR. Current concept of stem cell therapy for spinal cord injury: A review. Korean J Neurotrauma 2016; 12(2): 40-6.
  2. Richardson PM, McGuinness UM, Aguayo AJ. Peripheral nerve autografts to the rat spinal cord: Studies with axonal tracing methods. Brain Res 1982; 237(1): 147-62.
  3. Bregman BS, Reier PJ. Neural tissue transplants rescue axotomized rubrospinal cells from retrograde death. J Comp Neurol 1986; 244(1): 86-95.
  4. Siahmard Z, Alaei H, Reisi P, Pilehvarian A. Evaluation of the effects of red grape juice on Alzheimer's disease in rats. J Isfahan Med Sch 2012; 29(167): 2383-90. [In Persian].
  5. Ghorbani Alvanegh A, Tavallaei M, Edalat H. Evaluating the epigenetic effects of the miR17/92 cluster in noninvasive screening of genetically-based respiratory diseases. J Mil Med 2018; 20(1): 116-26. [In Persian].
  6. Alvanegh AG, Edalat H, Fallah P, Tavallaei M. Decreased expression of miR-20a and miR-92a in the serum from sulfur mustard-exposed patients during the chronic phase of resulting illness. Inhal Toxicol 2015; 27(13): 682-8.
  7. Ansari MH, Irani S, Edalat H, Amin R, Mohammadi RA. Deregulation of miR-93 and miR-143 in human esophageal cancer. Tumour Biol 2016; 37(3): 3097-103.
  8. Aasdi A, Erfanian Omidvar A. Restoring the stepping-like movement in spinal rat by electrical micro-stimulation of motor primitive blocks. J Isfahan Med Sch 2013; 31(250): 1324-38. [In Persian].
  9. Esfandiary E. The effects of traditional wooden toothbrush on improvement of constipation in patients with spinal cord injury. J Isfahan Med Sch 2014; 31(263): 1994-6. [In Persian].
  10. Esrafilian A, Karimi MT, Amiri P, Sadigh MJ. Walking performance of subjects with spinal cord injury using the new MTK reciprocal gait orthosis. J Isfahan Med Sch 2012; 30(185): 465-76. [In Persian].
  11. Mousavi SA, Kooshki M, Mehrabi Kooshki A. Physical and mental illness in capable in compare to disable veterans with spinal cord injury. J Isfahan Med Sch 2011; 29(145): 831-9. [In Persian].
  12. Kajouri A, Mojtahedi H, Salamat MR, Marandi SM, Siavash M. Comparison of bone mineral density of athletes and non-athletes in spinal cord injured veterans. J Isfahan Med Sch 2012; 30(176): 40-50. [In Persian].
  13. Mothe AJ, Tator CH. Advances in stem cell therapy for spinal cord injury. J Clin Invest 2012; 122(11): 3824-34.
  14. Muheremu A, Peng J, Ao Q. Stem cell based therapies for spinal cord injury. Tissue Cell 2016; 48(4): 328-33.
  15. Deng J, Zhang Y, Xie Y, Zhang L, Tang P. Cell Transplantation for Spinal Cord Injury: Tumorigenicity of Induced Pluripotent Stem Cell-Derived Neural Stem/Progenitor Cells. Stem Cells Int 2018; 2018: 5653787.
  16. Lee-Kubli CA, Lu P. Induced pluripotent stem cell-derived neural stem cell therapies for spinal cord injury. Neural Regen Res 2015; 10(1): 10-6.
  17. Zhang F. Structure-function evaluation of stem cell therapies for spinal cord injury. Curr Stem Cell Res Ther 2018; 13(3): 202-14.
  18. Alsanie WF, Niclis JC, Petratos S. Human embryonic stem cell-derived oligodendrocytes: Protocols and perspectives. Stem Cells Dev 2013; 22(18): 2459-76.
  19. Thomas KE, Moon LD. Will stem cell therapies be safe and effective for treating spinal cord injuries? Br Med Bull 2011; 98: 127-42.
  20. Kim SU, Lee HJ, Kim YB. Neural stem cell-based treatment for neurodegenerative diseases. Neuropathology 2013; 33(5): 491-504.
  21. Zhu Y, Uezono N, Yasui T, Nakashima K. Neural stem cell therapy aiming at better functional recovery after spinal cord injury. Dev Dyn 2018; 247(1): 75-84.
  22. Lo B, Parham L. Ethical issues in stem cell research. Endocr Rev 2009; 30(3): 204-13.
  23. Schimke MM, Marozin S, Lepperdinger G. Patient-specific age: The other side of the coin in advanced mesenchymal stem cell therapy. Front Physiol 2015; 6: 362.
  24. Martinez AM, Goulart CO, Ramalho BS, Oliveira JT, Almeida FM. Neurotrauma and mesenchymal stem cells treatment: From experimental studies to clinical trials. World J Stem Cells 2014; 6(2): 179-94.
  25. Doulames VM, Plant GW. Induced pluripotent stem cell therapies for cervical spinal cord injury. Int J Mol Sci 2016; 17(4): 530.
  26. Nagoshi N, Okano H. Applications of induced pluripotent stem cell technologies in spinal cord injury. J Neurochem 2017; 141(6): 848-60.
  27. Chhabra HS, Sarda K. Clinical translation of stem cell based interventions for spinal cord injury - Are we there yet? Adv Drug Deliv Rev 2017; 120: 41-9.
  28. Angelos MG, Kaufman DS. Pluripotent stem cell applications for regenerative medicine. Curr Opin Organ Transplant 2015; 20(6): 663-70.
  29. Bulic-Jakus F, Katusic BA, Juric-Lekic G, Vlahovic M, Sincic N. Teratoma: From spontaneous tumors to the pluripotency/malignancy assay. Wiley Interdiscip Rev Dev Biol 2016; 5(2): 186-209.
  30. Ng TK, Fortino VR, Pelaez D, Cheung HS. Progress of mesenchymal stem cell therapy for neural and retinal diseases. World J Stem Cells 2014; 6(2): 111-9.
  31. Dlouhy BJ, Awe O, Rao RC, Kirby PA, Hitchon PW. Autograft-derived spinal cord mass following olfactory mucosal cell transplantation in a spinal cord injury patient: Case report. J Neurosurg Spine 2014; 21(4): 618-22.
  32. Jin X, Lin T, Xu Y. Stem cell therapy and immunological rejection in animal models. Curr Mol Pharmacol 2016; 9(4): 284-8.
  33. Hofstetter CP, Holmstrom NA, Lilja JA, Schweinhardt P, Hao J, Spenger C, et al. Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome. Nat Neurosci 2005; 8(3): 346-53.
  34. Hendricks WA, Pak ES, Owensby JP, Menta KJ, Glazova M, Moretto J, et al. Predifferentiated embryonic stem cells prevent chronic pain behaviors and restore sensory function following spinal cord injury in mice. Mol Med 2006; 12(1-3): 34-46.
  35. Shihabuddin LS, Horner PJ, Ray J, Gage FH. Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus. J Neurosci 2000; 20(23): 8727-35.
  36. Song H, Stevens CF, Gage FH. Astroglia induce neurogenesis from adult neural stem cells. Nature 2002; 417(6884): 39-44.
  37. Wyatt LA, Keirstead HS. Stem cell-based treatments for spinal cord injury. Prog Brain Res 2012; 201: 233-52.
  38. Reeves A, Keirstead HS. Stem cell based strategies for spinal cord injury repair. Adv Exp Med Biol 2012; 760: 16-24.
  39. Oliveri RS, Bello S, Biering-Sorensen F. Mesenchymal stem cells improve locomotor recovery in traumatic spinal cord injury: systematic review with meta-analyses of rat models. Neurobiol Dis 2014; 62: 338-53.
  40. Volarevic V, Erceg S, Bhattacharya SS, Stojkovic P, Horner P, Stojkovic M. Stem cell-based therapy for spinal cord injury. Cell Transplant 2013; 22(8): 1309-23.
  41. Janowska J, Gargas J, Ziemka-Nalecz M, Zalewska T, Buzanska L, Sypecka J. Directed glial differentiation and transdifferentiation for neural tissue regeneration. Exp Neurol 2018. [Epub ahead of print].
  42. Pesaresi M, Sebastian-Perez R, Cosma MP. Dedifferentiation, transdifferentiation and cell fusion: In vivo reprogramming strategies for regenerative medicine. FEBS J 2018. [Epub ahead of print].
  43. Szabo E, Rampalli S, Risueno RM, Schnerch A, Mitchell R, Fiebig-Comyn A, et al. Direct conversion of human fibroblasts to multilineage blood progenitors. Nature 2010; 468(7323): 521-6.
  44. Marro S, Pang ZP, Yang N, Tsai MC, Qu K, Chang HY, et al. Direct lineage conversion of terminally differentiated hepatocytes to functional neurons. Cell Stem Cell 2011; 9(4): 374-82.
  45. Son EY, Ichida JK, Wainger BJ, Toma JS, Rafuse VF, Woolf CJ, et al. Conversion of mouse and human fibroblasts into functional spinal motor neurons. Cell Stem Cell 2011; 9(3): 205-18.
  46. Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Sudhof TC, Wernig M. Direct conversion of fibroblasts to functional neurons by defined factors. Nature 2010; 463(7284): 1035-41.
  47. Masip M, Veiga A, Izpisua Belmonte JC, Simon C. Reprogramming with defined factors: from induced pluripotency to induced transdifferentiation. Mol Hum Reprod 2010; 16(11): 856-68.
  48. Lujan E, Chanda S, Ahlenius H, Sudhof TC, Wernig M. Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cells. Proc Natl Acad Sci U S A 2012; 109(7): 2527-32.
  49. Elliott D, I, Tam R, Sefton MV, Shoichet MS. Cell and biomolecule delivery for tissue repair and regeneration in the central nervous system. J Control Release 2014; 190: 219-27.
  50. Mojadadi MSh, Golmohammadi R, Khanahmad H, Gholami O. Evaluating the effect of IL-27-transfected mesenchymal stem cells on certain histological and immunological parameters in a mouse model of experimental autoimmune encephalomyelitis. J Isfahan Med Sch 2013; 31(249): 1270-84. [In Persian].
  51. Edalat H, Hajebrahimi Z, Movahedin M, Tavallaei M, Amiri S, Mowla SJ. p75NTR suppression in rat bone marrow stromal stem cells significantly reduced their rate of apoptosis during neural differentiation. Neurosci Lett 2011; 498(1): 15-9.
  52. Edalat H, Hajebrahimi Z, Pirhajati V, Movahedin M, Tavallaei M, Soroush MR, et al. Transplanting p75-suppressed bone marrow stromal cells promotes functional behavior in a rat model of spinal cord injury. Iran Biomed J 2013; 17(3): 140-5.
  53. Edalat H, Hajebrahimi Z, Pirhajati V, Tavallaei M, Movahedin M, Mowla SJ. Exogenous expression of Nt-3 and TrkC genes in bone marrow stromal cells elevated the survival rate of the cells in the course of neural differentiation. Cell Mol Neurobiol 2017; 37(7): 1187-94.
  54. Eve DJ. Disease and stem cell-based analysis of the 2014 ASNTR meeting. Cell Med 2015; 7(3): 133-42.
  55. Fan L, Liu C, Chen X, Zou Y, Zhou Z, Lin C, et al. Directing induced pluripotent stem cell derived neural stem cell fate with a three-dimensional biomimetic hydrogel for spinal cord injury repair. ACS Appl Mater Interfaces 2018; 10(21): 17742-55.
  56. Ruff CA, Wilcox JT, Fehlings MG. Cell-based transplantation strategies to promote plasticity following spinal cord injury. Exp Neurol 2012; 235(1): 78-90.
Journal of Isfahan Medical School
Volume 36, Issue 501 - Serial Number 501
September and October 2017
Pages 1297-1307

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History

  • Receive Date: 03 November 2018
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

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