An examination of the mechanisms by which neural precursors augment recovery following spinal cord injury: A key role for remyelination

Cell Transplantation

Volumn 23, Issue 3, 2014, Pages 365-380

  Hawryluk, Gregory W J ^a,b   Spano, Stefania ^a,b   Chew, Derek ^a,b   Wang, Shelly ^b   Erwin, Mark ^a,b   Chamankhah, Mahmood ^b   Forgione, Nicole ^b   Fehlings, Michael G ^a,b,c  

^a UNIVERSITY HEALTH NETWORK   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c TORONTO WESTERN HOSPITAL   (Canada)

Author keywords

Mechanism; Neural precursor cells (NPCs); Remyelination; Spinal cord injury (SCI); Transplantation

Indexed keywords

CYCLOSPORIN; MINOCYCLINE; MYELIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL MATURATION; CONTROLLED STUDY; CYST; ELECTRON MICROSCOPY; FEMALE; INFLAMMATORY CELL; MOTOR PERFORMANCE; NERVE CELL; NERVE FIBER; NEURAL PRECURSOR CELL; NEURAL PRECURSOR CELL TRANSPLANTATION; NONHUMAN; OLIGODENDROGLIA; PRIORITY JOURNAL; RAT; REMYELINIZATION; SPINAL CORD INJURY; STEM CELL; STEM CELL TRANSPLANTATION; SURVIVAL; WHITE MATTER;

ANIMALS; CELL ADHESION MOLECULES; CELLS, CULTURED; FEMALE; MICE; MYELIN SHEATH; NERVE TISSUE PROTEINS; NEURAL STEM CELLS; OLIGODENDROGLIA; RATS; RATS, WISTAR; RECOVERY OF FUNCTION; SPINAL CORD; SPINAL CORD INJURIES;

EID: 84895880513     PISSN: 09636897     EISSN: None     Source Type: Journal    
DOI: 10.3727/096368912X662408     Document Type: Article

References (75)

1. Abercrombie, M. Estimation of nuclear population from microtome sections. Anat. Rec. 94:239-247; 1946.
2. Akiyama, Y.; Radtke, C.; Honmou, O.; Kocsis, J. D. Remyelination of the spinal cord following intravenous delivery of bone marrow cells. Glia 39(3):229-236; 2002.
3. Akiyama, Y.; Radtke, C.; Kocsis, J. D. Remyelination of the rat spinal cord by transplantation of identified bone marrow stromal cells. J. Neurosci. 22(15):6623-6630; 2002.
4. Andrews, E. M.; Tsai, S. Y.; Johnson, S. C.; Farrer, J. R.; Wagner, J. P.; Kopen, G. C.; Kartje, G. L. Human adult bone marrow-derived somatic cell therapy results in functional recovery and axonal plasticity following stroke in the rat. Exp. Neurol. 211(2):588-592; 2008.
5. Bambakidis, N. C.; Miller, R. H. Transplantation of oligodendrocyte precursors and sonic hedgehog results in improved function and white matter sparing in the spinal cords of adult rats after contusion. Spine J. 4(1):16-26; 2004.
6. Basso, D. M.; Beattie, M. S.; Bresnahan, J. C. A sensitive and reliable locomotor rating scale for open field testing in rats. J. Neurotrauma 12(1):1-21; 1995.
7. Bielekova, B.; Goodwin, B.; Richert, N.; Cortese, I.; Kondo, T.; Afshar, G.; Gran, B.; Eaton, J.; Antel, J.; Frank, J. A.; McFarland, H. F.; Martin, R. Encephalitogenic potential of the myelin basic protein peptide (amino acids 83-99) in multiple sclerosis: Results of a phase II clinical trial with an altered peptide ligand. Nat. Med. 6(10):1167-1175; 2000.
8. Bregman, B. S.; Coumans, J. V.; Dai, H. N.; Kuhn, P. L.; Lynskey, J.; McAtee, M.; Sandhu, F. Transplants and neurotrophic factors increase regeneration and recovery of function after spinal cord injury. Prog. Brain Res. 137:257-273; 2002.
9. Brundin, P.; Barker, R. A.; Parmar, M. Neural grafting in Parkinson's disease Problems and possibilities. Prog. Brain Res. 184:265-294; 2010.
10. Chen, J.; Li, Y.; Katakowski, M.; Chen, X.; Wang, L.; Lu, D.; Lu, M.; Gautam, S. C.; Chopp, M. Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat. J. Neurosci. Res. 73(6):778-786; 2003.
11. Chen, X.; Wang, X. D.; Chen, G.; Lin, W. W.; Yao, J.; Gu, X. S. Study of in vivo differentiation of rat bone marrow stromal cells into schwann cell-like cells. Microsurgery 26(2):111-115; 2006.
12. Choi, Y.; Kim, H. S.; Shin, K. Y.; Kim, E. M.; Kim, M.; Park, C. H.; Jeong, Y. H.; Yoo, J.; Lee, J. P.; Chang, K. A.; Kim, S.; Suh, Y. H. Minocycline attenuates neuronal cell death and improves cognitive impairment in Alzheimer's disease models. Neuropsychopharmacology 32(11):2393-2404; 2007.
13. Cummings, B. J.; Uchida, N.; Tamaki, S. J.; Salazar, D. L.; Hooshmand, M.; Summers, R.; Gage, F. H.; Anderson, A. J. Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice. Proc. Natl. Acad. Sci. USA 102(39):14069-14074; 2005.
14. Dasari, V. R.; Spomar, D. G.; Gondi, C. S.; Sloffer, C. A.; Saving, K. L.; Gujrati, M.; Rao, J. S.; Dinh, D. H. Axonal remyelination by cord blood stem cells after spinal cord injury. J. Neurotrauma 24(2):391-410; 2007.
15. Eftekharpour, E.; Karimi-Abdolrezaee, S.; Wang, J.; El Beheiry, H.; Morshead, C.; Fehlings, M. G. Myelination of congenitally dysmyelinated spinal cord axons by adult neural precursor cells results in formation of nodes of Ranvier and improved axonal conduction. J. Neurosci. 27(13):3416-3428; 2007.
16. Enzmann, G. U.; Benton, R. L.; Talbott, J. F.; Cao, Q.; Whittemore, S. R. Functional considerations of stem cell transplantation therapy for spinal cord repair. J. Neurotrauma 23(3-4):479-495; 2006.
17. Franklin, R. J.; Ffrench-Constant, C. Remyelination in the CNS: From biology to therapy. Nat. Rev. Neurosci. 9(11):839-855; 2008.
18. Fuhrmann, T.; Montzka, K.; Hillen, L. M.; Hodde, D.; Dreier, A.; Bozkurt, A.; Woltje, M.; Brook, G. A. Axon growth-promoting properties of human bone marrow mesenchymal stromal cells. Neurosci. Lett. 474(1):37-41; 2010.
19. Gogarten, W.; Van Aken, H.; Moskopp, D.; Roos, N.; Schleef, J.; Marcus, M.; Meyer, J. A case of severe cerebral trauma in a patient under chronic treatment with cyclosporine A. J. Neurosurg. Anesthesiol. 10(2):101-105; 1998.
20. Guest, J. D.; Hiester, E. D.; Bunge, R. P. Demyelination and Schwann cell responses adjacent to injury epicenter cavities following chronic human spinal cord injury. Exp. Neurol. 192(2):384-393; 2005.
21. Hawryluk, G. W.; Fehlings, M. G. The center of the spinal cord may be central to its repair. Cell Stem Cell 3(3):230-232; 2008.
22. Hawryluk, G. W.; Mothe, A.; Wang, J.; Wang, S.; Tator, C.; Fehlings, M. G. An in vivo characterization of trophic factor production following neural precursor cell or bone marrow stromal cell transplantation for spinal cord injury. Stem Cells Dev. 21(12):2222-2238; 2012.
23. Hawryluk, G. W.; Mothe, A. J.; Chamankhah, M.; Wang, J.; Tator, C.; Fehlings, M. G. In vitro characterization of trophic factor expression in neural precursor cells. Stem Cells Dev. 21(3):432-447; 2012.
24. Hawryluk, G. W.; Rowland, J.; Kwon, B. K.; Fehlings, M. G. Protection and repair of the injured spinal cord: A review of completed, ongoing, and planned clinical trials for acute spinal cord injury. Neurosurg. Focus 25(5):E14; 2008.
25. Hooshmand, M. J.; Sontag, C. J.; Uchida, N.; Tamaki, S.; Anderson, A. J.; Cummings, B. J. Analysis of host-mediated repair mechanisms after human CNS-stem cell transplantation for spinal cord injury: Correlation of engraftment with recovery. PLoS One 4(6):e5871; 2009.
26. Huang, J. K.; Jarjour, A. A.; Nait Oumesmar, B.; Kerninon, C.; Williams, A.; Krezel, W.; Kagechika, H.; Bauer, J.; Zhao, C.; Evercooren, A. B.; Chambon, P.; Ffrench-Constant, C.; Franklin, R. J. Retinoid X receptor gamma signaling accelerates CNS remyelination. Nat. Neurosci. 14(1):45-53; 2011.
27. Hunt, J.; Cheng, A.; Hoyles, A.; Jervis, E.; Morshead, C. M. Cyclosporin A has direct effects on adult neural precursor cells. J. Neurosci. 30(8):2888-2896; 2010.
28. Isele, N. B.; Lee, H. S.; Landshamer, S.; Straube, A.; Padovan, C. S.; Plesnila, N.; Culmsee, C. Bone marrow stromal cells mediate protection through stimulation of PI3-K/Akt and MAPK signaling in neurons. Neurochem. Int. 50(1):243-250; 2007.
29. Kappos, L.; Comi, G.; Panitch, H.; Oger, J.; Antel, J.; Conlon, P.; Steinman, L. Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial. The Altered Peptide Ligand in Relapsing MS Study Group. Nat. Med. 6(10):1176-1182; 2000.
30. Karimi-Abdolrezaee, S.; Eftekharpour, E.; Wang, J.; Morshead, C. M.; Fehlings, M. G. Delayed transplantation of adult neural precursor cells promotes remyelination and functional neurological recovery after spinal cord injury. J. Neurosci. 26(13):3377-3389; 2006.
31. Keirstead, H. S.; Nistor, G.; Bernal, G.; Totoiu, M.; Cloutier, F.; Sharp, K.; Steward, O. Human embryonic stem cellderived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J. Neurosci. 25(19):4694-4705; 2005.
32. Kernt, M.; Neubauer, A. S.; Eibl, K. H.; Wolf, A.; Ulbig, M. W.; Kampik, A.; Hirneiss, C. Minocycline is cytoprotective in human trabecular meshwork cells and optic nerve head astrocytes by increasing expression of XIAP, survivin, and Bcl-2. Clin. Ophthalmol. 4:591-604; 2010.
33. Kirkpatrick, L. L.; Witt, A. S.; Payne, H. R.; Shine, H. D.; Brady, S. T. Changes in microtubule stability and density in myelin-deficient shiverer mouse CNS axons. J. Neurosci. 21(7):2288-2297; 2001.
34. Koshizuka, S.; Okada, S.; Okawa, A.; Koda, M.; Murasawa, M.; Hashimoto, M.; Kamada, T.; Yoshinaga, K.; Murakami, M.; Moriya, H.; Yamazaki, M. 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. 63(1):64-72; 2004.
35. Lasiene, J.; Shupe, L.; Perlmutter, S.; Horner, P. No evidence for chronic demyelination in spared axons after spinal cord injury in a mouse. J. Neurosci. 28(15):3887-3896; 2008.
36. Lee, J. H.; Chung, W. H.; Kang, E. H.; Chung, D. J.; Choi, C. B.; Chang, H. S.; Hwang, S. H.; Han, H.; Choe, B. Y.; Kim, H. Y. Schwann cell-like remyelination following transplantation of human umbilical cord blood (hUCB)-derived mesenchymal stem cells in dogs with acute spinal cord injury. J. Neurol. Sci. 300(1-2):86-96; 2011.
37. Luo, J.; Bo, X.; Wu, D.; Yeh, J.; Richardson, P. M.; Zhang, Y. Promoting survival, migration, and integration of transplanted Schwann cells by over-expressing polysialic acid. Glia 59(3):424-434; 2011.
38. Mazzeo, A. T.; Brophy, G. M.; Gilman, C. B.; Alves, O. L.; Robles, J. R.; Hayes, R. L.; Povlishock, J. T.; Bullock, M. R. Safety and tolerability of cyclosporin a in severe traumatic brain injury patients: Results from a prospective randomized trial. J. Neurotrauma 26(12):2195-2206; 2009.
39. McDonald, J. W.; Belegu, V. Demyelination and remyelination after spinal cord injury. J. Neurotrauma 23(3-4):345-359; 2006.
40. Modo, M.; Stroemer, R. P.; Tang, E.; Patel, S.; Hodges, H. Effects of implantation site of dead stem cells in rats with stroke damage. Neuroreport 14(1):39-42; 2003.
41. Ogawa, Y.; Sawamoto, K.; Miyata, T.; Miyao, S.; Watanabe, M.; Nakamura, M.; Bregman, B. S.; Koike, M.; Uchiyama, Y.; Toyama, Y.; Okano, H. 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. 69(6):925-933; 2002.
42. Ohta, M.; Suzuki, Y.; Noda, T.; Ejiri, Y.; Dezawa, M.; Kataoka, K.; Chou, H.; Ishikawa, N.; Matsumoto, N.; Iwashita, Y.; Mizuta, E.; Kuno, S.; Ide, C. Bone marrow stromal cells infused into the cerebrospinal fluid promote functional recovery of the injured rat spinal cord with reduced cavity formation. Exp. Neurol. 187(2):266-278; 2004.
43. Okano, H.; Ogawa, Y.; Nakamura, M.; Kaneko, S.; Iwanami, A.; Toyama, Y. Transplantation of neural stem cells into the spinal cord after injury. Semin. Cell Dev. Biol. 14(3):191-198; 2003.
44. Osaka, M.; Honmou, O.; Murakami, T.; Nonaka, T.; Houkin, K.; Hamada, H.; Kocsis, J. D. Intravenous administration of mesenchymal stem cells derived from bone marrow after contusive spinal cord injury improves functional outcome. Brain Res. 1343:226-235; 2010.
45. Parr, A. M.; Kulbatsk, I.; Zahir, T.; Wang, X.; Yue, C.; Keating, A.; Tator, C. H. Transplanted adult spinal cordderived neural stem/progenitor cells promote early functional recovery after rat spinal cord injury. Neuroscience 155(3):760-770; 2008.
46. Parr, A. M.; Tator, C. H.; Keating, A. Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury. Bone Marrow Transplant. 40(7):609-619; 2007.
47. Pearse, D. D.; Sanchez, A. R.; Pereira, F. C.; Andrade, C. M.; Puzis, R.; Pressman, Y.; Golden, K.; Kitay, B. M.; Blits, B.; Wood, P. M.; Bunge, M. B. Transplantation of Schwann cells and/or olfactory ensheathing glia into the contused spinal cord: Survival, migration, axon association, and functional recovery. Glia 55(9):976-1000; 2007.
48. Popovich, P. G. Immunological regulation of neuronal degeneration and regeneration in the injured spinal cord. Prog. Brain Res. 128:43-58; 2000.
49. Rivera, F. J.; Steffenhagen, C.; Kremer, D.; Kandasamy, M.; Sandner, B.; Couillard-Despres, S.; Weidner, N.; Kury, P.; Aigner, L. Deciphering the oligodendrogenic program of neural progenitors: Cell intrinsic and extrinsic regulators. Stem Cells Dev. 19(5):595-606.
50. Rivlin, A. S.; Tator, C. H. Effect of duration of acute spinal cord compression in a new acute cord injury model in the rat. Surg. Neurol. 10(1):38-43; 1978.
51. Roach, A.; Boylan, K.; Horvath, S.; Prusiner, S. B.; Hood, L. E. Characterization of cloned cDNA representing rat myelin basic protein: Absence of expression in brain of shiverer mutant mice. Cell 34(3):799-806; 1983.
52. Rossi, S. L.; Keirstead, H. S. Stem cells and spinal cord regeneration. Curr. Opin. Biotechnol. 20(5):552-562; 2009.
53. Rossi, S. L.; Nistor, G.; Wyatt, T.; Yin, H. Z.; Poole, A. J.; Weiss, J. H.; Gardener, M. J.; Dijkstra, S.; Fischer, D. F.; Keirstead, H. S. Histological and functional benefit following transplantation of motor neuron progenitors to the injured rat spinal cord. PLoS One 5(7):e11852; 2010.
54. Sasaki, M.; Honmou, O.; Akiyama, Y.; Uede, T.; Hashi, K.; Kocsis, J. D. Transplantation of an acutely isolated bone marrow fraction repairs demyelinated adult rat spinal cord axons. Glia 35(1):26-34; 2001.
55. Scheff, S. W.; Saucier, D. A.; Cain, M. E. A statistical method for analyzing rating scale data: The BBB locomotor score. J. Neurotrauma 19(10):1251-1260; 2002.
56. Sharp, J.; Frame, J.; Siegenthaler, M.; Nistor, G.; Keirstead, H. S. Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants improve recovery after cervical spinal cord injury. Stem Cells 28(1):152-163; 2010.
57. Sheth, R. N.; Manzano, G.; Li, X.; Levi, A. D. Transplantation of human bone marrow-derived stromal cells into the contused spinal cord of nude rats. J. Neurosurg. Spine 8(2):153-162; 2008.
58. Shi, E.; Jiang, X.; Wang, L.; Akuzawa, S.; Nakajima, Y.; Kazui, T. Intrathecal injection of hepatocyte growth factor gene-modified marrow stromal cells attenuates neurologic injury induced by transient spinal cord ischemia in rabbits. Anesthesiology 113(5):1109-1117; 2010.
59. Steinman, L. Antigen-specific therapy of multiple sclerosis: The long-sought magic bullet. Neurotherapeutics 4(4):661-665; 2007.
60. Steward, O.; Zheng, B.; Tessier-Lavigne, M. False resurrections: Distinguishing regenerated from spared axons in the injured central nervous system. J. Comp. Neurol. 459(1):1-8; 2003.
61. Sykova, E.; Jendelova, P. In vivo tracking of stem cells in brain and spinal cord injury. Prog. Brain Res. 161:367-383; 2007.
62. Takahashi, Y.; Tsuji, O.; Kumagai, G.; Hara, C. M.; Okano, H. J.; Miyawaki, A.; Toyama, Y.; Okano, H.; Nakamura, M. Comparative study of methods for administering neural stem/progenitor cells to treat spinal cord injury in mice. Cell Transplant. 20(5):727-739; 2011.
63. Targett, M. P.; Sussman, J.; Scolding, N.; O'Leary, M. T.; Compston, D. A.; Blakemore, W. F. Failure to achieve remyelination of demyelinated rat axons following transplantation of glial cells obtained from the adult human brain. Neuropathol. Appl. Neurobiol. 22(3):199-206; 1996.
64. Tate, C. C.; Fonck, C.; McGrogan, M.; Case, C. C. Human mesenchymal stromal cells and their derivative, SB623 cells, rescue neural cells via trophic support following in vitro ischemia. Cell Transplant. 19(8):973-984; 2010.
65. Tetzlaff, W.; Okon, E. B.; Karimi-Abdolrezaee, S.; Hill, C. E.; Sparling, J. S.; Plemel, J. R.; Plunet, W. T.; Tsai, E. C.; Baptiste, D.; Smithson, L. J.;Kawaja, M. D.; Fehlings, M. G.; Kwon, B. K. A Systematic Review of Cellular Transplantation Therapies for Spinal Cord Injury. J. Neurotrauma 28(8):1611-1682; 2011.
66. Tropepe, V.; Sibilia, M.; Ciruna, B. G.; Rossant, J.; Wagner, E. F.; van der Kooy, D. Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon. Dev. Biol. 208(1):166-188; 1999.
67. Vaquero, J.; Zurita, M. Functional recovery after severe CNS trauma: Current perspectives for cell therapy with bone marrow stromal cells. Prog. Neurobiol. 93(3):341-349; 2011.
68. Wang, X.; Luo, E.; Li, Y.; Hu, J. Schwann-like mesenchymal stem cells within vein graft facilitate facial nerve regeneration and remyelination. Brain Res. 1383:71-80; 2011.
69. Warren, K. G.; Catz, I.; Ferenczi, L. Z.; Krantz, M. J. Intravenous synthetic peptide MBP8298 delayed disease progression in an HLA Class II-defined cohort of patients with progressive multiple sclerosis: Results of a 24-month double-blind placebo-controlled clinical trial and 5 years of follow-up treatment. Eur. J. Neurol. 13(8):887-895; 2006.
70. Wright, K. T.; El Masri, W.; Osman, A.; Chowdhury, J.; Johnson, W. E. Bone marrow for the treatment of spinal cord injury: Mechanisms and clinical application. Stem Cells 29(2):169-178; 2011.
71. Wu, S.; Suzuki, Y.; Ejiri, Y.; Noda, T.; Bai, H.; Kitada, M.; Kataoka, K.; Ohta, M.; Chou, H.; Ide, C. Bone marrow stromal cells enhance differentiation of cocultured neurosphere cells and promote regeneration of injured spinal cord. J. Neurosci. Res. 72(3):343-351; 2003.
72. Yasuda, A.; Tsuji, O.; Shibata, S.; Nori, S.; Takano, M.; Kobayashi, Y.; Takahashi, Y.; Fujiyoshi, K.; Hara, C. M.; Miyawaki, A.;Okano, H. J.; Toyama, Y.; Nakamura, M.; Okano, H. Significance of remyelination by neural stem/ progenitor cells transplanted into the injured spinal cord. Stem Cells 29(12):1983-1994; 2011.
73. Yune, T. Y.; Lee, J. Y.; Jung, G. Y.; Kim, S. J.; Jiang, M. H.; Kim, Y. C.; Oh, Y. J.; Markelonis, G. J.; Oh, T. H. Minocycline alleviates death of oligodendrocytes by inhibiting pro-nerve growth factor production in microglia after spinal cord injury. J. Neurosci. 27(29):7751-7761; 2007.
74. Zeng, X.; Zeng, Y. S.; Ma, Y. H.; Lu, L. Y.; Du, B. L.; Zhang, W.; Li, Y.; Chan, W. Y. Bone Marrow Mesenchymal Stem Cells in a Three Dimensional Gelatin Sponge Scaffold Attenuate Inflammation, Promote Angiogenesis and Reduce Cavity Formation in Experimental Spinal Cord Injury. Cell Transplant. 20(11-12):1881-1899; 2011.
75. Zhao, F. Q.; Zhang, P. X.; He, X. J.; Du, C.; Fu, Z. G.; Zhang, D. Y.; Jiang, B. G. Study on the adoption of Schwann cell phenotype by bone marrow stromal cells in vitro and in vivo. Biomed. Environ. Sci. 18(5):326-333; 2005.