Subarachnoid Space Transplantation of Schwann and/or Olfactory Ensheathing Cells Following Severe Spinal Cord Injury Fails to Improve Locomotor Recovery in Rats
-
Mohsen Nategh
,
Masoumeh Firouzi
,
Mehdi Naji-Tehrani
,
Leila Oryadi Zanjani
,
Zahra Hassannejad
,
Mohammad Hosein Nabian
,
Shayan Abdollah Zadegan
,
Mehrbod Karimi
,
Vafa Rahimi-Movaghar
Abstract
Treatment of spinal cord injury by exogenous cells has brought both successful and unsuccessful results. Olfactory ensheathing cells and Schwann cells have been widely used for transplantation purposes. In this study, we investigated the effects of these cells on contused spinal cord by introducing cells into subarachnoid space. Fifty thousand Schwann cells or olfactory ensheathing cells or a mixture of both cell types were transplanted one week after a 3-second clip compression injury at T-9 spinal cord level in rats. Starting from the day one of spinal cord injury, animals were assessed for six months by BBB test and then were sacrificed for immunohistochemistry labeling of the spinal cord injury site. There was no locomotor recovery in any of the treatment groups including controls. Immunohistochemistry assessment indicated positive labeling of P75 and S100 markers in the cell-transplanted groups compared with control. Our data suggest that transplantation of Schwann cells and/or olfactory ensheathing cells into the subarachnoid space does not improve motor recovery in severely injured spinal cord, at least with the number of cells transplanted here. This, however, should not be regarded as an essentially negative outcome, and further studies which consider higher densities of cells are required.
Barnett SC, Riddell JS. Olfactory ensheathing cells (OECs) and the treatment of CNS injury: advantages and possible caveats. Journal of Anatomy 2004; 204: 57–67.
Fortuna J, Hill CE, Bunge MB. Combinatorial strategies with Schwann cell transplantation to improve repair of the injured spinal cord. Neuroscience Letters 2009; 456: 124–32.
Oudega M. Schwann cell and olfactory ensheathing cell implantation for repair of the contused spinal cord. Acta Physiologica (Oxford) 2007; 189(2): 181-9.
Franklin RJ. Remyelination of the demyelinated CNS: The case for and against transplantation of central, peripheral and olfactory glia. Brain Research Bulletin [Review] 2002; 57(6): 827–32.
Ban DX, Kong XH, Feng SQ, Ning GZ, Chen JT, Guo SF. Intraspinal cord graft of autologous activated Schwann cells efficiently promotes axonal regeneration and functional recovery after rat's spinal cord injury. Brain Research 2009; 1256: 149-61.
Blakemore WF. Limited remyelination of CNS axons by Schwann cells transplanted into the sub-arachnoid space. Journal of the Neurological Sciences 1984; 64: 265–76.
Lavdas AA, Papastefanaki F, Thomaidou D, Matsas R. Schwann cell transplantation for CNS repair. Current Medical Chemistry 2008; 15(2): 151-60.
Pearse DD, Pereira FC, Marcillo AE, Bates ML, Berrocal YA, Filbin MT, et al. cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury. Nature Medicine 2004; 10(6): 610-6.
Pearse DD, Sanchez AR, Pereira FC, Andrade CM, Puzis R, Pressman Y, et al. Transplantation of Schwann cells and/or olfactory ensheathing glia into the contused spinal cord: Survival, migration, axon association, and functional recovery. Glia 2007; 55(9): 976-1000.
Plant GW, Christensen CL, Oudega M, Bunge MB. Delayed transplantation of olfactory ensheathing glia promotes sparing/regeneration of supraspinal axons in the contused adult rat spinal cord. Journal of Neurotrauma 2003; 20(1): 1-16.
Raisman G. Repair of spinal cord injury by transplantation of olfactory ensheathing cells. Comptes Rendus Biologies 2007; 330: 557–60.
Lopez-Vales R, Fores J, Navarro X, Verdu E. Chronic transplantation of olfactory ensheathing cells promotes partial recovery after complete spinal cord transection in the rat. Glia 2007; 55(3): 303-11.
Lu J, Feron F, Mackay-Sim A, Waite PM. Olfactory ensheathing cells promote locomotor recovery after delayed transplantation into transected spinal cord. Brain 2002; 125(Pt 1): 14-21.
Keyvan-Fouladi N, Raisman G, Li Y. Functional repair of the corticospinal tract by delayed transplantation of olfactory ensheathing cells in adult rats. The Journal of Neuroscience 2003; 23(28): 9428-34.
Iwashita Y, Blakemore WF. Areas of demyelination do not attract significant numbers of Schwann cells transplanted into normal white matter. Glia 2000; 31: 232–40.
Iwashita Y, Fawcett JW, Crang AJ, Franklin RJM, Blakemore WF. Schwann cells transplanted into normal and X-irradiated adult white matter do not migrate extensively and show poor long-term survival. Experimental Neurology 2000; 164: 292–302.
Miyagoe-Suzuki Y, Nakagawa M, Takeda S. Merosin and Congenital Muscular Dystrophy. Microscopy Research and Technique 2000; 48: 181–91.
Vroemen M, Caioni M, Bogdahn U, Weidner N. Failure of Schwann cells as supporting cells for adult neural progenitor cell grafts in the acutely injured spinal cord. Cell and Tissue Research 2007; 327(1): 1-13.
Pearse DD, Marcillo AE, Oudega M, Lynch MP, Wood PM, Bunge MB. Transplantation of Schwann cells and olfactory ensheathing glia after spinal cord injury: does pretreatment with methylprednisolone and interleukin-10 enhance recovery? Journal of Neurotrauma 2004; 21(9): 1223-39.
Cao L, Zhu YL, Su Z, Lv B, Huang Z, Mu L, et al. Olfactory ensheathing cells promote migration of Schwann cells by secreted nerve growth factor. Glia 2007 Jul; 55(9): 897-904.
Firouzi M, Moshayedi P, Saberi H, Mobasheri H, Abolhassani F, Jahanzad I, et al. Transplantation of Schwann cells to subarachnoid space induces repair in contused rat spinal cord. Neuroscience Letters 2006; 402: 66–70.
Saberi H, Moshayedi P, Aghayan HR, Arjmand B, Hosseini SK, Emami-Razavi SH, et al. Treatment of chronic thoracic spinal cord injury patients with autologous Schwann cell transplantation: an interim report on safety considerations and possible outcomes. Neuroscience Letters 2008; 443(1): 46-50.
Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. Journal of Neurotrauma 1995; 12: 1-21.
Takami T, Oudega M, Bates ML, Wood PM, Kleitman N, Bunge MB. Schwann cell but not olfactory ensheathing glia transplants improve hindlimb locomotor performance in the moderately contused adult rat thoracic spinal cord. The Journal of Neuroscience 2002; 22(15): 6670-81.
Nash HH, Borke RC, Anders JJ. Ensheathing cells and methylprednisolone promote axonal regeneration and functional recovery in the lesioned adult rat spinal cord. The Journal of Neuroscience 2002; 22(16): 7111-20.
Ghosh M, Tuesta LM, Puentes R, Patel S, Melendez K, El Maarouf A, et al. Extensive cell migration, axon regeneration, and improved function with polysialic acid-modified Schwann cells after spinal cord injury. Glia 2012; 60(6): 979-92.
Silva NA, Sousa RA, Pires AO, Sousa N, Salgado AJ, Reis RL. Interactions between Schwann and olfactory ensheathing cells with a starch/polycaprolactone scaffold aimed at spinal cord injury repair. Journal of Biomedical Materials Research A 2011; 100: 470–6.
Wang H, Liu C, Ma X. Alginic acid sodium hydrogel co-transplantation with Schwann cells for rat spinal cord repair. Archives of Medical Sciences 2012; 8(3): 563-8.
Wang JM, Zeng YS, Wu JL, Li Y, Teng YD. Cograft of neural stem cells and schwann cells overexpressing TrkC and neurotrophin-3 respectively after rat spinal cord transection. Biomaterials 2011; 32(30): 7454-68.
Franklin RJM, Blakemore WF. Requirements for Schwann cell migration within CNS environments: A viewpoint. International Journal of Developmental Neuroscience 1993; 11: 641–9.
Deumens R, Koopmans GC, Honig WM, Maquet V, Jerome R, Steinbusch HW, et al. Chronically injured corticospinal axons do not cross large spinal lesion gaps after a multifactorial transplantation strategy using olfactory ensheathing cell/olfactory nerve fibroblast-biomatrix bridges. Journal of Neuroscience Research 2006; 83(5): 811-20.
Lu P, Yang H, Culbertson M, Graham L, Roskams AJ, Tuszynski MH. Olfactory ensheathing cells do not exhibit unique migratory or axonal growth-promoting properties after spinal cord injury. The Journal of Neuroscience 2006; 26(43): 11120-30.
Steward O, Sharp K, Selvan G, Hadden A, Hofstadter M, Au E, et al. A re-assessment of the consequences of delayed transplantation of olfactory lamina propria following complete spinal cord transection in rats. Experimental Neurology 2006; 198(2): 483-99.
Deumens R, Van Gorp SF, Bozkurt A, Beckmann C, Fuhrmann T, Montzka K, et al. Motor outcome and allodynia are largely unaffected by novel olfactory ensheathing cell grafts to repair low-thoracic lesion gaps in the adult rat spinal cord. Behav Brain Res 2013 Jan 15; 237: 185-9.
Lang BC, Zhang Z, Lv LY, Liu J, Wang TY, Yang LH, et al. OECs transplantation results in neuropathic pain associated with BDNF regulating ERK activity in rats following cord hemisection. BMC Neurosci 2013; 14: 80.
Tabakow P, Jarmundowicz W, Czapiga B, Fortuna W, Miedzybrodzki R, Czyz M, et al. Transplantation of Autologous Olfactory Ensheathing Cells in Complete Human Spinal Cord Injury. Cell Transplantation 2013; 22: 1591–612.
Rahimi-Movaghar V, Yazdi A, Karimi M, Mohammadi M, Firouzi M, Zanjani LO, et al. Effect of decompression on complete spinal cord injury in rats. International Journal of Neuroscience 2008; 118(10): 1359-73.
Mayeur A, Duclos C, Honore A, Gauberti M, Drouot L, do Rego JC, et al. Potential of olfactory ensheathing cells from different sources for spinal cord repair. PLoS One 2013; 8(4): e62860.
Hill CE, Hurtado A, Blits B, Bahr BA, Wood PM, Bunge MB, et al. Early necrosis and apoptosis of Schwann cells transplanted into the injured rat spinal cord. European Journal of Neuroscience 2007; 26: 1433–45.
Toft A, Scott DT, Barnett SC, Riddell JS. Electrophysiological evidence that olfactory cell transplants improve function after spinal cord injury. Brain 2007; 130: 970-84.
Fouad K, Krajacic A, Tetzlaff W. Spinal cord injury and plasticity: Opportunities and challenges. Brain Research Bulletin 2011; 84: 237-42.
Schucht P, Raineteau O, Schwab ME, Fouad K. Anatomical correlates of loco-motor recovery following dorsal and ventral lesions of the rat spinal cord. Experimental Neurology 2002; 176: 143–53.
Casha S, Yu WR, Fehlings MG. Oligodendroglial apoptosis occurs along degenerating axons and is associated with FAS and p75 expression following spinal cord injury in the rat. Neuroscience 2001; 103(1): 203-18.
Ohtani R, Tomimoto H, Wakita H, Kitaguchi H, Nakaji K, Takahashi R. Expression of S100 protein and protective effect of arundic acid on the rat brain in chronic cerebral hypoperfusion. Brain Research 2007; 1135(1): 195-200.
Ramo´n-Cueto A, Nieto-Sampedro M. Regeneration into the spinal cord of transected dorsal root axons is promoted by ensheathing glia transplants. Experimental Neurology 1994; 127: 232–44.
Vincent AJ, Taylor JM, Choi-Lundberg DL, West AK, Chuah MI. Genetic Expression Profile of Olfactory Ensheathing Cells Is Distinct From That of Schwann Cells and Astrocytes. Glia 2005; 51: 132–47.
Lindsay SL, Riddell JS, S.C. B. Olfactory mucosa for transplant-mediated repair: a complex tissue for a complex injury? Glia 2010; 58: 125-34.
Tetzlaff W, Okon EB, Karimi-Abdolrezaee S, Hill CE, Sparling JS, Plemel JR, et al. A Systematic Review of Cellular Transplantation Therapies for Spinal Cord Injury. Journal of Neurotrauma 2011; 28(8): 1611-82.
Centenaro LA, da Cunha Jaeger M, Ilha J, de Souza MA, Balbinot LF, do Nascimento PS, et al. Implications of olfactory lamina propria transplantation on hyperreflexia and myelinated fiber regeneration in rats with complete spinal cord transection. Neurochem Res 2013 Feb; 38(2): 371-81.
Barnett SC, Riddell JS. Olfactory ensheathing cell transplantation as a strategy for spinal cord repair—what can it achieve? Nature Clinical Practice Neurology 2007; 3(3): 152-61.
Ban DX, Ning GZ, Feng SQ, Wang Y, Zhou XH, Liu Y, et al. Combination of activated Schwann cells with bone mesenchymal stem cells: the best cell strategy for repair after spinal cord injury in rats. Regenerative Medicine 2011; 6(6): 707-20.
| Files | ||
| Issue | Vol 54, No 9 (2016) | |
| Section | Original Article(s) | |
| Keywords | ||
| Spinal cord compression Cell therapy Behavioral recovery | ||
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