Stem cell-based therapy for spinal cord injury

Cell Transplantation

Volumn 22, Issue 8, 2013, Pages 1309-1323

  Volarevic, Vladislav ^a   Erceg, Slaven ^b,c   Bhattacharya, Shom Shanker ^b   Stojkovic, Petra ^a,c   Horner, Philip ^d   Stojkovic, Miodrag ^a,c  

^a UNIVERSITY OF KRAGUJEVAC   (Serbia)

^b CABIMER Andalusian Center for Molecular Biology and Regenerative Medicine CSIC University of Seville UPO   (Spain)

^c Institute for Stem Cell and Regenerative Medicine ^*

^d UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

Differentiation; Inflammation; Remyelination; Spinal cord injury (SCI); Stem cells (SCs)

Indexed keywords

FAS LIGAND; FREE RADICAL; GLUTAMIC ACID; INTERLEUKIN 1ALPHA; INTERLEUKIN 1BETA; MONOCYTE CHEMOTACTIC PROTEIN 1; NEUROTROPHIN 3; TUMOR NECROSIS FACTOR ALPHA;

ADULT STEM CELL; ASTROCYTE; AUTOTRANSPLANTATION; BLOOD BRAIN BARRIER; CARCINOGENESIS; CARCINOGENICITY; CELL DEATH; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL SURVIVAL; DENTATE GYRUS; EMBRYONIC STEM CELL; EXCITOTOXICITY; HUMAN; LOCOMOTION; MEMBRANE PERMEABILITY; MESENCHYMAL STEM CELL; MICROGLIA; MOTONEURON; MOTOR ACTIVITY; NERVE FIBER GROWTH; NERVE REGENERATION; NERVOUS SYSTEM INFLAMMATION; NEURAL STEM CELL; NEUROPATHIC PAIN; NONHUMAN; OLFACTORY ENSHEATHING CELL; OLIGODENDROGLIA; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; REMYELINIZATION; REVIEW; RUBROSPINAL TRACT; SCHWANN CELL; SPINAL CORD INJURY; STEM CELL TRANSPLANTATION; SUBVENTRICULAR ZONE; UMBILICAL CORD BLOOD;

ANIMALS; HUMANS; SPINAL CORD INJURIES; STEM CELL TRANSPLANTATION; STEM CELLS;

EID: 84881004447     PISSN: 09636897     EISSN: None     Source Type: Journal    
DOI: 10.3727/096368912X657260     Document Type: Review

References (120)

1. Ankeny, D. P.; Popovich, P. G,B cells and autoantibodies: Complex roles in CNS injury. Trends Immunol. 31:332- 338; 2010.
2. Babcock, A. A.; Kuziel, W. A.; Rivest, S.; Owens, T. Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS. J. Neurosci. 23:7922- 7930; 2003.
3. Babu, H.; Cheung, G.; Kettenmann, H.; Palmer, T. D.; Kempermann, G. Enriched monolayer precursor cell cultures from micro-dissected adult mouse dentate gyrus yield functional granule cell-like neurons. PLoS One 2:e388; 2007.
4. Baizabal, J. M.; Covarrubias, L. The embryonic midbrain directs neuronal specification of embryonic stem cells at early stages of differentiation. Dev. Biol. 325:49-59; 2009.
5. Bakiri, Y.; Hamilton, N. B.; Káradóttir, R.; Attwell, D. Testing NMDA receptor block as a therapeutic strategy for reducing ischaemic damage to CNS white matter. Glia 56:233-240; 2008.
6. Barnabé-Heider, F.; Frisen, J. Stem cells for spinal cord repair. Cell Stem Cell 3:16-24; 2008.
7. Beattie, M. S.; Hermann, G. E.; Rogers, R. C.; Bresnahan, J. C. Cell death in models of spinal cord injury. Prog. Brain Res. 137:37-47; 2002.
8. Brederlau, A.; Correia, A. S.; Anisimov, S. V.; Elmi, M.; Paul, G.; Roybon, L.; Morizane, A.; Bergquist, F.; Riebe, I.; Nannmark, U.; Carta, M.; Hanse, E.; Takahashi, J.; Sasai, Y.; Funa, K.; Brundin, P.; Eriksson, P. S.; Li, J. Y. Transplantation of human embryonic stem cell-derived cells to a rat model of Parkinson's disease: Effect of in vitro differentiation on graft survival and teratoma formation. Stem Cells 24:1433-1440; 2006.
9. Calancie, B.; Madsen, P. W.; Wood, P.; Marcillo, A. E.; Levi, A. D.; Bunge, R. P. A guidance channel seeded with autologous Schwann cells for repair of cauda equina injury in a primate model. J. Spinal Cord Med. 32:379- 388; 2009.
10. Callera, F.; do Nascimento, R. X. 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. 34:130-131; 2006.
11. Cao, Q.; He, Q.; Wang, Y.; Cheng, X.; Howard, R. M.; Zhang, Y.; DeVries, W. H.; Shields, C. B.; Magnuson, D. S.; Xu, X. M.; Kim, D. H.; Whittemore, S. R. Transplantation of ciliary neurotrophic factor-expressing adult oligodendrocyte precursor cells promotes remyelination and functional recovery after spinal cord injury. J. Neurosci. 30:2989-3001; 2010.
12. Casha, S.; Yu, W. R.; Fehlings, M. G. Oligodendroglial apoptosis occurs along degenerating axons and is associated with FAS and p75 expression following spinal cord injury in the rat. Neuroscience 103:203-218; 2001.
13. Chambers, S. M.; Fasano, C.; Papapetrou, E. P.; Tomishima, M.; Sadelain, M, Studer, L,Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat. Biotechnol. 27:275-280; 2009.
14. Chernykh, E. R.; Stupak, V. V.; Muradov, G. M; Sizikov, M. Y; Shevela, E. Y.; Leplina, O. Y.; Tikhonova, M. A.; Kulagin, A. D.; Lisukov, I. A.; Ostanin, A. A.; Kozlov, V. A. Application of autologous bone marrow stem cells in the therapy of spinal cord injury patients. Bull. Exp. Biol. Med. 143:543-547; 2007.
15. Cote, M. P.; Amin, A. A.; Tom, V. J.; Houle, J. D. Peripheral nerve grafts support regeneration after spinal cord injury. Neurotherapeutics 8:294-303; 2011.
16. Coutts, M.; Keirstead, H. S. Stem cells for the treatment of spinal cord injury. Exp. Neurol. 209:368-377; 2008.
17. Cristante, A. F.; Barros-Filho, T. E.; Tatsui, N.; Mendrone, A.; Caldas, J. G.; Camargo, A.; Alexandre, A.; Teixeira, W. G.; Oliveira, R. P.; Marcon, R. M. Stem cells in the treatment of chronic spinal cord injury: Evaluation of somatosensitive evoked potentials in 39 patients. Spinal Cord 47:733-738; 2009.
18. 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 102:14069-14074; 2005.
19. Davidoff, G.; Thomas, P.; Johnson, M.; Berent, S.; Dijkers, M.; Doljanac, R. Closed head injury in acute traumatic spinal cord injury: Incidence and risk factors, Arch. Phys. Med. Rehabil. 69:869-873; 1988.
20. Davies, J. E.; Huang, C.; Proschel, C.; Noble, M.; Mayer Proschel, M.; Davies, S. J. Astrocytes derived from glial restricted precursors promote spinal cord repair. J. Biol. 5:7; 2006.
21. Deda, H.; Inci, M. C.; Kürekçi, A. E.; Kayihan, K.; Ozgün, E.; Ustünsoy, G. E.; Kocabay, S. Treatment of chronic spinal cord injured patients with autologous bone marrowderived hematopoietic stem cell transplantation: 1-year follow-up. Cytotherapy 10:565-574; 2008.
22. Deng, Y. B.; Liu, Y.; Zhu, W. B.; Bi, X. B.; Wang, Y. Z.; Ye, M. H.; Zhou, G. Q. The cotransplantation of human bone marrow stromal cells and embryo olfactory ensheathing cells as a new approach to treat spinal cord injury in a rat model. Cytotherapy 10:551-564; 2008.
23. Dimos, J. T.; Rodolfa, K. T.; Niakan, K. K.; Weisenthal, L. M.; Mitsumoto, H.; Chung, W.; Croft, G. F.; Saphier, G.; Leibel, R.; Goland, R.; Wichterle, H.; Henderson, C. E.; Eggan, K. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321:1218-1221; 2008.
24. Dougherty, K. J.; Hochman, S. Spinal cord injury causes plasticity in a subpopulation of lamina I GABAergic interneurons. J. Neurophysiol. 100:212-223; 2008.
25. Erceg, S.; Ronaghi, M.; Oria, M.; Roselló, M. G.; Aragó, M. A.; Lopez, M. G.; Radojevic, I.; Moreno-Manzano, V.; Rodríguez-Jiménez, F. J.; Bhattacharya, S. S.; Cordoba, J.; Stojkovic, M. Transplanted oligodendrocytes and motoneuron progenitors generated from human embryonic stem cells promote locomotor recovery after spinal cord transection. Stem Cells 28:1541-1549; 2010.
26. Erceg, S.; Ronaghi, M.; Stojkovic, M. Human embryonic stem cell differentiation toward regional specific neural precursors. Stem Cells 27:78-87; 2009.
27. Feron, F.; Perry, C.; Cochrane, J.; Licina, P.; Nowitzke, A.; Urquhart, S.; Geraghty, T.; Mackay-Sim, A. Autologous olfactory ensheathing cell transplantation in human spinal cord injury. Brain 128:2951-2960; 2005.
28. Fouad, K.; Schnell, L.; Bunge, M. B.; Schwab, M. E.; Liebscher, T.; Pearse, D. D. Combining Schwann cell bridges and olfactory-ensheathing glia grafts with chondroitinase promotes locomotor recovery after complete transaction of the spinal cord. J. Neurosci. 25:1169-1178; 2005.
29. Franssen, E. H.; de Bree, F. M.; Verhaagen, J. Olfactory ensheathing glia: Their contribution to primary olfactory nervous system regeneration and their regenerative potential following transplantation into the injured spinal cord. Brain Res. Rev. 56:236-258; 2007.
30. García-Alias, G.; Lopez-Vales, R.; Fores, J.; Navarro, X.; Verdu, E. Acute transplantation of olfactory ensheathing cells or Schwann cells promotes recovery after spinal cord injury in the rat. J. Neurosci. Res. 75:632-641; 2004.
31. Genovese, T.; Cuzzocrea, S. Role of free radicals and poly (ADP-ribose) polymerase-1 in the development of spinal cord injury: New potential therapeutic targets. Curr. Med. Chem. 15:477-487; 2008.
32. Gil, J. E.; Woo, D. H.; Shim, J. H.; Kim, S. E.; You, H. J.; Park, S. H.; Paek, S. H.; Kim, S. K.; Kim, J. H. Vitronectin promotes oligodendrocyte differentiation during neurogenesis of human embryonic stem cells. FEBS Lett. 583:561-567; 2009.
33. Gris, P.; Tighe, A.; Levin, D.; Sharma, R.; Brown, A. Transcriptional regulation of scar gene expression in primary astrocytes. Glia 55:1145-1155; 2007.
34. Gros, T.; Sakamoto, J. S.; Blesch, A.; Havton, L. A.; Tuszynski, M. H. Regeneration of long-tract axons through sites of spinal cord injury using templated agarose scaffolds. Biomaterials 31:6719-6729; 2010.
35. Hall, E.; Springer, J,Neuroprotection and acute spinal cord injury: A reappraisal. NeuroRx 1:80-100; 2004.
36. Hawryluk, G.; Fehlings, M. The center of the spinal cord may be central to its repair. Cell Stem Cell 3:230-232; 2008.
37. Hermann, A.; Gastl, R.; Liebau, S.; Popa, M. O.; Fiedler, J.; Boehm, B. O.; Maisel, M.; Lerche, H.; Schwarz, J.; Brenner, R.; Storch A. Efficient generation of neural stem cell like cells from adult human bone marrow stromal cells. J. Cell Sci. 117; 4411-4422; 2004.
38. Hernandez, J.; Torres-Espin, A.; Navarro, X. Adult stem cell transplants for spinal cord injury repair: Current state in preclinical research. Curr. Stem Cell Res. Ther. 6:273- 287; 2011.
39. 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:e5871; 2009.
40. Hsu, Y. C.; Lee, D. C.; Chiu, I. M. Neural stem cells, neural progenitors, and neurotrophic factors. Cell Transplant. 16:133-150; 2007.
41. Hyun, J. K.; Kim, H. W. Clinical and experimental advances in regeneration of spinal cord injury. J. Tissue Eng. 1(1):650857; 2010.
42. Imaizumi, T.; Lankford, K. L.; Waxman, S. G.; Greer, C. A.; Kocsis, J. D. Transplanted olfactory ensheathing cells remyelinate and enhance axonal conduction in the demyelinated dorsal columns of the rat spinal cord. J. Neurosci. 18:6176-6185; 1998.
43. Iwanami, A.; Kaneko, S.; Nakamura, M.; Kanemura, Y.; Mori, H.; Kobayashi, S.; Yamasaki, M.; Momoshima, S.; Ishii, H.; Ando, K.; Tanioka, Y.; Tamaoki, N.; Nomura, T.; Toyama, Y.; Okano, H. Transplantation of human neural stem cells for spinal cord injury in primates. J. Neurosci. Res. 80:182-190; 2005.
44. Jain, A.; Kim, Y. T.; McKeon, R. J.; Bellamkonda, R. V. In situ gelling hydrogels for conformal repair of spinal cord defects, and local delivery of BDNF after spinal cord injury. Biomaterials 27:497-504; 2006.
45. Jeffery, N. D.; Hamilton, L.; Granger, N. Designing clinical trials in canine spinal cord injury as a model to translate successful laboratory interventions into clinical practice. Vet. Rec. 168:102-107; 2011.
46. Jung, D. I.; Ha, J.; Kang, B. T.; Kim, J. W.; Quan, F. S.; Lee, J. H.; Woo, E. J.; Park, H. M. A comparison of autologous and allogenic bone marrow-derived mesenchymal stem cell transplantation in canine spinal cord injury. J. Neurol. Sci. 285:67-77; 2009.
47. Kang, K. S.; Kim, S. W.; Oh, Y. H.; Yu, J. W.; Kim, K. Y.; Park, H. K.; Song, C. H.; Han, H. 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 7:368-373; 2005.
48. 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. 26:3377-3389; 2006.
49. Keilhoff, G.; Goihl, A.; Stang, F.; Wolf, G.; Fansa, H. Peripheral nerve tissue engineering: Autologous Schwann cells vs. transdifferentiated mesenchymal stem cells. Tissue Eng. 12:1451-1465; 2006.
50. Keirstead, H. S.; Nistor, G.; Bernal, G.; Totoiu, M.; Cloutier, F.; Sharp, K.; Steward, O. Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J. Neurosci. 25:4694-4705; 2005.
51. Kettenmann, H.; Hanisch, U. K.; Noda, M.; Verkhratsky, A. Physiology of microglia. Physiol. Rev. 91:461-553; 2001.
52. Kim, B. G.; Hwang, D. H.; Lee, S. I.; Kim, E. J.; Kim, S. U. Stem cell-based cell therapy for spinal cord injury. Cell Transplant. 16:355-364; 2007.
53. Kim, H. J.; Lee, H. J.; Kim, S. H. Therapeutic effects of human mesenchymal stem cells on traumatic brain injury in rats: Secretion of neurotrophic factors and inhibition of apoptosis. J. Neurotrauma 27:131-138; 2010.
54. Kirschner, D. A.; Avila, R. L.; Gamez-Sazo, R. E.; Luoma, A.; Enzmann, G. U.; Agrawal, D.; Inouye, H.; Bunge, M. B.; Kocsis, J.; Peters, A.; Whittemore, S. R. Rapid assessment of internodal myelin integrity in central nervous system tissue. J. Neurosci. Res. 88:712-721; 2010.
55. Krampera, M.; Glennie, S.; Dyson, J.; Scott, D.; Laylor, R.; Simpson, E.; Dazzi E. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood 101:3722-3729; 2003
56. Kubasak, M. D.; Jindrich, D. L.; Zhong, H.; Takeoka, A.; McFarland, K. C.; Munoz-Quiles, C.; Roy, R. R.; Edgerton, V. R.; Ramon-Cueto, A.; Phelps, P. OEG implantation and step training enhance hindlimb-stepping ability in adult spinal transected rats. Brain 131:264-276; 2008.
57. Kumar, A.; Kumar, S.; 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. 7:241- 248; 2009.
58. Lakatos, A.; Barnett, S. C.; Franklin, R. J. Olfactory ensheathing cells induce less host astrocyte response and chondroitin sulphate proteoglycan expression than Schwann cells following transplantation into adult CNS white matter. Exp. Neurol. 184:237-246; 2003.
59. Lakatos, A.; Franklin, R. J.; Barnett, S. C. Olfactory ensheathing cells and Schwann cells differ in their in vitro interactions with astrocytes. Glia 32:214-225; 2000.
60. Lako, M.; Armstrong, L.; Stojkovic, M. Induced pluripotent stem cells: It looks simple but can looks deceive? Stem Cells 28:845-850; 2010.
61. 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. 28:3887-3896; 2008.
62. Le Blanc, K.; Tammik, C.; Rosendahl, K.; Zetterberg, E.; Ringden, O. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp. Hematol. 31:890-896; 2003.
63. Lee, H.; Shamy, G. A; Elkabetz, Y.; Schofield, C. M.; Harrsion, N. L.; Panagiotakos, G.; Socci, N. D.; Tabar, V.; Studer, L. Directed differentiation and transplantation of human embryonic stem cell-derived motoneurons. Stem Cells 25:1931-1939; 2007.
64. Li, J. Y.; Christophersen, N. S.; Hall, V.; Soulet, D.; Brundin, P. Critical issues of clinical human embryonic stem cell therapy for brain repair. Trends Neurosci. 31:146-153; 2008.
65. Li, Y.; Field, P. M.; Raisman, G. Repair of adult rat corticospinal tract by transplants of olfactory ensheathing cells. Science 277:2000-2002; 1997.
66. Li, Y.; Sauve, Y.; Li, D.; Lund, R. D.; Raisman, G. Transplanted olfactory ensheathing cells promote regeneration of cut adult rat optic nerve axons. J. Neurosci. 23:7783-7788; 2003.
67. Lim, P. A.; Tow, A. M,Recovery and regeneration after spinal cord injury: A review and summary of recent literature. Ann. Acad. Med. Singapore 36:49-57; 2007.
68. Lima, C.; Pratas-Vital, J.; Escada, P.; Hasse-Ferreira, A.; Capucho, C.; Peduzzi, J. D. Olfactory mucosa autografts in human spinal cord injury: A pilot clinical study. J. Spinal Cord Med. 29:191-203; 2006.
69. Little, J. W.; Ditunno, J. F.; Stiens, S. A; Harris, R. M. Incomplete spinal cord injury: Neuronal mechanisms of motor recovery and hyperreflexia. Arch. Phys. Med. Rehabil. 80:587-599; 1999.
70. McDonald, J. W.; Sadowsky, C. Spinal-cord injury. Lancet 359:417-425; 2002.
71. Meletis, K.; Barnabé-Heider, F.; Carlén, M.; Evergren, E.; Tomilin, N.; Shupliakov, O.; Frisén, J. Spinal cord injury reveals multilineage differentiation of ependymal cells. PLoS Biol. 6:e182; 2008.
72. Miura, K.; Okada, Y.; Aoi, T.; Okada, A.; Takahashi, K.; Okita, K.; Nakagawa, M.; Koyanagi, M.; Tanabe, K.; Ohnuki, M.; Ogawa, D.; Ikeda, E.; Okano, H.; Yamanaka, S. Variation in the safety of induced pluripotent stem cell lines. Nat. Biotechnol. 27:743-745; 2009.
73. Moalem, G.; Gdalyahu, A.; Shani, Y.; Otten, U.; Lazarovici, P.; Cohen, I. R.; Schwartz, M. Production of neurotrophins by activated T cells: Implications for neuroprotective autoimmunity. J. Autoimmun. 15:331-345; 2000.
74. Moreno-Manzano, V.; Rodríguez-Jiménez, F. J.; García Roselló, M.; Laínez, S.; Erceg, S.; Calvo, M. T.; Ronaghi, M.; Lloret, M.; Planells-Cases, R.; Sánchez-Puelles, J. M.; Stojkovic, M. Activated spinal cord ependymal stem cells rescue neurological function. Stem Cells 27:733-743; 2009.
75. Moviglia, G. A.; Fernandez-Viña, R.; Brizuela, J. A.; Saslavsky, J.; Vrsalovic, F.; Varela, G.; Bastos, F.; Farina, P.; Etchegaray, G.; Barbieri, M.; Martinez, G.; Picasso, F.; Schmidt, Y.; Brizuela, P.; Gaeta, C. A.; Costanzo, H.; Moviglia-Brandolino, M. T.; Merino, S.; Pes, M. E.; Veloso, M. J.; Rugilo, C.; Tamer, I.; Shuster, G. S. Combined protocol of cell therapy for chronic spinal cord injury. Report on the electrical and functional recovery of two patients. Cytotherapy 8:202-209; 2006.
76. Munoz-Quiles, C.; Santos-Benito, F. F.; Llamusí, M. B.; Ramon-Cueto, A.Chronic spinal injury repair by olfactory bulb ensheathing glia and feasibility for autologous therapy. J. Neuropathol. Exp. Neurol. 68:1294-1308; 2009.
77. Nash, H. H.; Borke, R. C; Anders, J. J. Ensheathing cells and methylprednisolone promote axonal regeneration and functional recovery in the lesioned adult rat spinal cord. J. Neurosci. 22:7111-7120; 2002.
78. Nistor, G. I.; Totoiu, M. O.; Haque, N.; Carpenter, M. K.; Keirstead, H. S. Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation. Glia 49:385-396; 2005.
79. Nomura, H.; Zahir, T.; Kim, H.; Katayama, Y.; Kulbatski, I.; Morshead, C. M.; Shoichet, M. S.; Tator, C. H. Extramedullary chitosan channels promote survival of transplanted neural stem and progenitor cells and create a tissue bridge after complete spinal cord transection. Tissue Eng. Part A 14:649-665; 2008.
80. Pal, R.; Venkataramana, N. K.; Bansal, A.; Balaraju, S.; Jan, M.; Chandra, R.; Dixit, A.; Rauthan, A.; Murgod, U.; Totey, S. Ex vivo expanded autologous bone marrowderived mesenchymal stromal cells in human spinal cord injury/paraplegia: A pilot clinical study. Cytotherapy 11:897-911; 2009.
81. Park, D. H.; Lee, J. H.; Borlongan, C. V.; Sanberg, P. R.; Chung, Y. G.; Cho, T. H. Transplantation of umbilical cord blood stem cells for treating spinal cord injury. Stem Cell Rev. 7:181-194; 2011.
82. Park, S.; Koh, S. E.; Maeng, S.; Lee, W. D.; Lim, J.; Lee, Y. J. Neural progenitors generated from the mesenchymal stem cells of first-trimester human placenta matured in the hypoxic-ischemic rat brain and mediated restoration of locomotor activity. Placenta 32:269-276; 2011.
83. Parr, A. M.; Kulbatski, 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 155:760-770; 2008.
84. 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 55:976-1000; 2007.
85. Petit, A.; Sellers, D. L.; Liebl, D. J.; Tessier-Lavigne, M.; Kennedy, T. E.; Horner P. J. Adult spinal cord progenitor cells are repelled by netrin-1 in the embryonic and injured adult spinal cord. Proc. Natl. Acad. Sci. USA 104:17837- 17842; 2007.
86. Pineau, I,Lacroix, S,Proinflammatory cytokine synthesis in the injured mouse spinal cord: Multiphasic expression pattern and identification of the cell types involved. J. Comp. Neurol. 500:267-285; 2007.
87. Pluchino, S.; Zanotti, L.; Rossi, B.; Brambilla, E.; Ottoboni, L.; Salani, G.; Martinello, M.; Cattalini, A.; Bergami, A.; Furlan, R.; Comi, G.; Constantin, G.; Martino, G. Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism. Nature 436:266-271; 2005.
88. Porada, C. D.; Zanjani, E. D.; Almeida-Porada, G. Adult mesenchymal stem cells: A pluripotent population with multiple applications. Curr. Stem Cell Res. Ther. 1:365- 369; 2006.
89. Radtke, C.; Sasaki, M.; Lankford, K. L.; Vogt, P. M.; Kocsis, J. D. Potential of olfactory ensheathing cells for cell-based therapy in spinal cord injury. J. Rehabil. Res. Dev. 45:141-151; 2008.
90. 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 25:425-435; 2000.
91. Ramon-Cueto, A.; Plant, G. W.; Avila, J.; Bunge, M. B. Long-distance axonal regeneration in the transected adult rat spinal cord is promoted by olfactory ensheathing glia transplants. J. Neurosci. 18:3803-3815; 1998.
92. Rowland, J. W.; Hawryluk, G. W.; Kwon, B.; Fehlings, M. G. Current status of acute spinal cord injury pathophysiology and emerging therapies: Promise on the horizon. Neurosurg. Focus 25:E2; 2008.
93. Ruff, C. A.; Wilcox, J. T.; Fehlings, M. G. Cell-based transplantation strategies to promote plasticity following spinal cord injury. Exp. Neurol. 235:78-90; 2012.
94. Ruitenberg, M. J.; Levison, D. B.; Lee, S. V.; Verhaagen, J.; Harvey, A. R.; Plant, G. W. NT-3 expression from engineered olfactory ensheathing glia promotes spinal sparing and regeneration. Brain 128:839-853; 2005.
95. Sasaki, M.; Radtke, C.; Tan, A. M.; Zhao, P.; Hamada, H.; Houkin, K.; Honmou, O.; Kocsis, J. D,BDNFhypersecreting human mesenchymal stem cells promote functional recovery, axonal sprouting, and protection of corticospinal neurons after spinal cord injury. J. Neurosci. 29:14932-14941; 2009.
96. Schwarz, S. C.; Schwarz, J. Translation of stem cell therapy for neurological diseases. Transl. Res. 156:155-160; 2010.
97. 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 28:152-163; 2010.
98. Stadtfeld, M.; Hochedlinger, K. Induced pluripotency: History, mechanisms, and applications. Genes Dev. 24:2239-2263; 2010.
99. Straley, K. S.; Foo, C. W.; Heilshorn, S. C. Biomaterial design strategies for the treatment of spinal cord injuries. J. Neurotrauma 27:1-19; 2010.
100. Syková, E.; Homola, A.; Mazanec, R.; Lachmann, H.; Konrádová S. L.; Kobylka, P.; Pádr, R.; Neuwirth, J.; Komrska, V.; Vávra, V.; Stulík, J.; Bojar, M. Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury. Cell Transplant. 15:675- 687; 2006.
101. Takahashi, K.; Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663-676; 2006.
102. Takeoka, A.; Jindrich, D. L.; Munoz-Quiles, C.; Zhong, H.; van den Brand, R.; Pham, D. L.; Ziegler, M. D.; RamónCueto, A.; Roy, R. R.; Edgerton, V. R.; Phelps, P. E. Axon regeneration can facilitate or suppress hindlimb function after olfactory ensheathing glia transplantation. J. Neurosci. 31:4298-4310; 2011.
103. Teng, Y. D.; Lavik, E. B.; Qu, X.; Park, K. I.; Ourednik, J.; Zurakowski, D.; Langer, R.; Snyder, E. Y. Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proc. Natl. Acad. Sci. USA 99:3024-3029; 2002.
104. Tetzlaff, C.; Okujeni, S.; Egert, U.; Wörgötter, F.; Butz, M. Self-organized criticality in developing neuronal networks. PLoS Comput. Biol. 6:e1001013; 2010.
105. 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 28:1611-1682; 2011.
106. Thuret, S.; Moon, L. D.; Gage, F. H. Therapeutic interventions after spinal cord injury. Nat. Rev. Neurosci. 7:628- 643; 2006.
107. Tobias, C. A.; Dhoot, N. O.; Wheatley, M. A.; Tessler, A.; Murray, M.; Fischer, I. Grafting of encapsulated BDNFproducing fibroblasts into the injured spinal cord without immune suppression in adult rats. J. Neurotrauma 18:287-301; 2001.
108. Tse, W.T.; Pendleton, J. D.; Beyer, W. M.; Egalka M. C.; Guinan, E. C. Suppression of allogeneic T cell proliferation by human marrow stromal cells: Implications in transplantation. Transplantation 75:389-397; 2003.
109. Tsuji, O.; Miura, K.; Okada, Y.; Fujiyoshi, K.; Mukaino, M.; Nagoshi, N.; Kitamura, K; Kumagai, G.; Nishino, M.; Tomisato, S.; Higashi, H.; Nagai, T.; Katoh, H.; Kohda, K.; Matsuzaki, Y.; Yuzaki, M.; Ikeda, E.; Toyama, Y.; Nakamura, M.; Yamanaka, S.; Okano, H. Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury. Proc. Natl. Acad. Sci. USA 107:12704-12709; 2010.
110. Wang, M.; Zhai, P.; Chen, X.; Schreyer, D. J.; Sun, X.; Cui F. Bioengineered scaffolds for spinal cord repair. Tissue. Eng. Part B Rev. 17:177-194; 2011.
111. Warren, L.; Manos, P.; Ahfeldt, T.; Loh, Y.; Li, H.; Lau, F.; Ebina, W.; Mandal, P.; Smith, Z.; Meissner, A.; Daley, G.; Brack, A.; Collins, J.; Cowan, C.; Schlaeger, T.; Rossi, D. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7:1-13; 2010.
112. Wernig, M.; Zhao, J. P.; Pruszak, J.; Hedlund, E.; Fu, D.; Soldner, F.; Broccoli, V.; Constantine-Paton, M.; Isacson, O.; Jaenisch, R. 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 105:5856-5861; 2008.
113. Wislet-Gendebien, S.; Wautier, F.; Leprince, P.; Rogister, B. Astrocytic and neuronal fate of mesenchymal stem cells expressing nestin. Brain Res. Bull. 68:95-102; 2005.
114. Woodside, J. R.; McGuire, E. J. Urethral hypotonicity after suprasacral spinal cord injury. J. Urol. 121:783-785; 1979.
115. Wright, L. S.; Prowse, K. R.; Wallace, K.; Linskens, M. H.; Svendsen, C. N. Human progenitor cells isolated from the developing cortex undergo decreased neurogenesis and eventual senescence following expansion in vitro. Exp. Cell Res. 312:2107-2120; 2006.
116. Wu, J.; Yoo, S.; Wilcock, D.; Lytle, J. M.; Leung, P. Y.; Colton, C. A.; Wrathall, J. R. Interaction of NG2(+) glial progenitors and microglia/macrophages from the injured spinal cord. Glia 58:410-422; 2010.
117. Wyndaele, M.; Wyndaele, J,Incidence prevalence and epidemiology of spinal cord injury: What learns a worldwide literature survey? Spinal Cord 44:523-529; 2006.
118. Yoon, S. H.; Shim, Y. S.; Park, Y. H.; Chung, J. K.; Nam, J. H.; Kim, M. O.; Park, H. C.; Park, S. R.; Min, B. H.; Kim, E. Y.; Choi, B. H.; Park, H.; Ha, Y.,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 25:2066-2073; 2007.
119. Yu, Y. L.; Chou, R. H.; Chen, L. T.; Shyu, W. C.; Hsieh, S. C.; Wu, C. S.; Zeng, H. J.; Yeh, S. P.; Yang, D. M.; Hung, S. C.; Hung, M. C. EZH2 regulates neuronal differentiation of mesenchymal stem cells through PIP5K1C-dependent calcium signaling. J. Biol. Chem. 286:9657-9667; 2011.
120. Zawadzka, M.; Rivers, L. E.; Fancy, S.; Zhao, C.; Tripathi, R.; Jamen, F.; Young, K.; Goncharevich, A.; Pohl, H.; Rizzi, M.; Rowitch, D. H.; Kessaris, N.; Suter, U.; Richardson, W.; Franklin, R. CNS-resident glial progenitor/stem cells produce Schwann cells as well as oligodendrocytes during repair of CNS demyelination. Cell Stem Cell 6:578-590; 2010.