Cellular therapy in amyotrophic lateral sclerosis;Terapia celular en la esclerosis lateral amiotrófica

Neurologia

Volumn 23, Issue 4, 2008, Pages 226-237

  Matías Guiu, Jorge ^a,c   Barcia, J A ^a   Garcia Verdugo J M ^b   Galan L ^a   Vela, A ^a   Garcia Ramos R ^a  

^a UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

^b UNIVERSITY OF VALENCIA   (Spain)

^c HOSPITAL CLÍNICO SAN CARLOS   (Spain)

Author keywords

Amyotrophic lateral sclerosis; Cellular therapy; Motor neuron disease; Neural stem cells; Stem cells

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; CARDIOTROPHIN 1; CILIARY NEUROTROPHIC FACTOR; COPPER ZINC SUPEROXIDE DISMUTASE; EPIDERMAL GROWTH FACTOR; GLIAL FIBRILLARY ACIDIC PROTEIN; GROWTH FACTOR; LEUKEMIA INHIBITORY FACTOR; NEUROTROPHIN 3; PLEIOTROPHIN; SCATTER FACTOR; SOMATOMEDIN C; VASCULOTROPIN;

AMYOTROPHIC LATERAL SCLEROSIS; CHOLINERGIC NERVE CELL; GENE MUTATION; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; MOTOR NEURON DISEASE; NERVE CELL DIFFERENTIATION; NEURAL STEM CELL; NONHUMAN; REVIEW; STEM CELL TRANSPLANTATION; SURVIVAL TIME; TRANSGENIC RAT;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; HUMANS; STEM CELL TRANSPLANTATION;

EID: 46049110987     PISSN: 02134853     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (132)

1. Charcot JM, Joffroy A. Deux cas d'atrophie musculaire progressive avec lesions de la substance gris et des faisceaux antero-lateraux de la moelle epineire. Arch Physiol Neurol Pathol 1869;2:744.
2. Matias-Guiu J, Galán L, García-Ramos R, Vela A, Guerrero A. Epidemiología descriptiva en esclerosis lateral amiotrófica. Neurología 2007;22:368-80.
3. Mulder D, Kurland L, Offord K, Beard C. Familiar adult motor neuron disease: amyotrophic lateral sclerosis. Neurology 1986;36:511-7.
4. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familiar amyotrophic lateral sclerosis. Nature 1993;362:59-62.
5. Lindvall O, Kokaia Z, Martínez-Serrano A. Stem cell therapy for human neurodegenerative disorders-how to make it work. Nat Med 2004;10(Suppl.):S42-50.
6. Silani V, Cova L, Corbo M, Ciammola A, Polio L. Stem-cell therapy for amyotrophic lateral sclerosis. Lancet 2004;364:200-2.
7. Clement AM, Nguyen MD, Roberts EA, Garcia ML, Boillee S, Rule M, et al. Wild-type non neuronal cells extended survival of SOD1 mutant motor neurons in ALS mice. Science 2003:302:113-7.
8. Boillee S, Yamanaka K, Lobsiger CS, Copeland NG, Jenkins NA, Kassiotis G, et al. Onset and progression in inherited ALS determined by motor neurons and microglia. Science 2006;312:1389-92.
9. Doetsch F, Caille I, Lim DA, García-Verdugo JM, Álvarez-Buylla A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 1999;97:703-16.
10. Morshead CM, Craig CG, van der Kooy D. In vivo clonal analyses reveal the properties of endogenous neural stem cell proliferation in the adult mammalian forebrain. Development 1998;125:2251-61.
11. Hermann A, Maisel M, Liebau S, Gerlach M, Kleger A, Schwartz J, et al. Mesodermal cell types induce neurogenesis from adult human hippocampal progenitor cells. J Neurochem 2006;98:629-40.
12. Samberg PR, Willing AE, Cahll DW. Novel cellular approaches to repair of neurodegenerative diseases from Sertoli cells to umbilical blood stem cells. Neurotox Res 2002;4:95-121.
13. Newman MB, Misiuta I, Willing AE, Zigova T, Karl RC, Borlongan CV, et al. Tumorogenicity issues of embryonic carcinoma-derived stem cells: relevance to surgical trials using NT2 and hNT neural cells. Stem Cells Dev 2005;14:29-43.
14. Corti S, Locatelli F, Papadimitriou D, Donadoni C, del Bo R, Fortunate F, et al. Multipotentiality, homing properties, and piramidal patogénesis of CNS-derived Le (seea-1)+/CXCR4+ stem cell. FASEB J 2005;9:1860-2.
15. Flax JD, Aurora S, Yang C, Simonin C, Willis AM, Billinghurts LL, et al. Engraftable human neural stem cells respond to developmental cues, replace neurons, and express foreign genes. Nat Biotechnol 1998;16:1033-9.
16. Brustle O, Choudhary K, Karram K, Küttner A, Murray K, Dubois-Dalcq M, et al. Chimeric brains generated by intraventricular transplantation of fetal human brain cells into embryonic rats. Nat Biotechnol 1998;16:1040-4.
17. Zhang SC, Wernig M, Duncan ID, Brustle O, Thomson JA. In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat Biotechnol 2001;19:1129-33.
18. Suhonen JO, Peterson DA, Ray J, Gage FH. Differentiation of adult hippocampus-derived progenitors into olfactory neurons in vivo. Nature 1996;383:624-7.
19. 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;20:8727-35.
20. Fricker RA, Carpenter MK, Winckler C, Greco C, Gates MA, Björklund A. Site-specific migration and neuronal differentiation of human neural progenitor cells after transplantation in the adult rat brain. J Neurosci 1999;19:5990-6005.
21. Sheen VL, Arnold MW, Wang Y, Macklis JD. Neural precursor differentiation following transplantation into neocortex is dependent on intrinsic developmental state and receptor competence. Exp Neurol 1999;158:47-62.
22. Pallini R, Vitiani LR, Bez A, Casalbore P, Facchiano F, Di Giorgi Gerevini V, et al. Homologous transplantation of neural stem cells to the injured spinal cord of mice. Neurosurgery 2005;57:1014-25.
23. Li XJ, Du ZW, Zarnowska ED, Pankratz M, Hansen LO, Pearce RA, et al. Specification of motoneurons from human embryonic stem cells. Nat Biotechnol 2005;23:215-21.
24. Miles GB, Yohn DC, Wichterle H, Jessell TM, Rafuse VF, Brownstone RM. Functional properties of motoneurons derived from mouse embryonic stem cells. J Neurosci 2004;24:7848-58.
25. Wichterle H, Lieberam I, Porter JA, Jessell TM. Directed differentiation of embryonic stem cells into motor neurons. Cell 2002;110:385-97.
26. Wu P, Tarasenko Y, Gu Y, Huang LM, Goggeshall RE, Yu Y. Region-specific generation of cholinergic neurons from fetal human neural stem cells graftet in adult rat. Nat Neurosci 2002;5:1271-8.
27. Gao J, Goggeshall RE, Tarasenko Y, Wu P. Human neural stem cell derived cholinergic neurons innervate muscle in motoneuron deficient adult rats. Neuroscience 2005;131:257-62.
28. Gao J, Goggeshall RE, Cheng JM, Wang J, Wu P. Functional motoneurons develop from human neural stem cell transplants in adults rats. Neuroreport 2007;18:565-9.
29. Craff MN, Zeballos JL, Johnson TS, Ranka MP, Howard R, Motarjem P, et al. Embryonic stem cell-derived motor neurons preserve muscle after peripheral nerve injury. Plast Reconstr Surg 2007;119:235-45.
30. Deshpande DM, Kim YS, Martinez T, Carmen J, Dike S, Shats I, et al. Recovery from paralysis in adult rats using embryonic stem cells. Ann Neurol 2006;60:32-44.
31. Hamada M, Yoshikawa H, Ueda Y, Kurokawa MS, Watanabe K, Sakakibara M, et al. Introduction of the MASH1 gene into mouse embryonic stem cells leads to differentiation of motoneuron precursors lacking Nogo receptor expression that can be applicable for transplantation to spinal cord injury. Neurobiol Dis 2006;22:509-22.
32. Soundararajan P, Lindsey BW, Leopold C, Rafuse VF. Easy and rapid differentiation of embryonic stem cells into functional motoneurons using sonic hedgehog-producing cells. Stem Cells 2007;25:1697-796.
33. Cummings BJ, Uchida N, Tamaki SJ, Salazar DL, Hooshmand M, Summers R, et al. Human neural stem cell differentiate and promote locomotor recovery in spinal cord-injured mice. Proc Natl Acad Sci USA 2005;102:14069-70.
34. Nayak MS, Kim Y, Goldman M, Keirstead HS, Kerr DA. Cellular therapies in motor neuron diseases. Biochim Biophys Acta 2006:1138-762.
35. Galán L, Vela A, Guerrero A, Barcia JA, García-Verdugo JM, Matías-Guiu J. Modelos experimentales en esclerosis lateral amiotrófica. Neurología 2007;22:381-8.
36. Janson CG, Ramesh TM, During MJ, Leone P, Heywood J. Human intrathecal transplantation of peripheral blood stem cells in amyotrophic lateral sclerosis. J Hematother Stem Cell Res 2001;10:913-5.
37. Mazzini L, Faglioli L, Boccatteli R, Mareschi K, Oliveri G, Olivieri C, et al. Stem cells therapy in amyotrofic lateral sclerosis: a methodological approach in humans. Amyotroph Lateral Scler other Motor Neuron Disord 2003;4:158-61.
38. Silani V, Leigh N. Stem cell therapy for ALS: hope and reality. Amyotroph Lateral Scler other Motor Neuron Disord 2003;4:8-10.
39. Swash M. Stem cell therapy in human ALS. Amyotroph Lateral Scler other Motor Neuron Disord 2003;4:133-4.
40. Mitchel JD, Borasio CG. Amyotrophic lateral Sclerosis. Lancet 2007;369:2031-41.
41. Mazzini L, Mareschi K, Ferrero I, Vassallo L, Oliveri G, Nasuelli N, et al. Stem cells treatment in amyotrophic lateral sclerosis. J Neurol Sci: Doi 10.1016/j.jns.2007.05.016.
42. Huang H, Tank K, Chen L, Xue Y, Wang H, Xi H, et al. MR spectroscopy evaluation and short-term outcome of olfactory enshealthing cells transplantation in amyotrophic lateral sclerosis patients. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2007;21:52-7 (abstract).
43. Ende N, Weinstein F, Chen R, Ende M. Human umbilical cord blood effect on sod mice (amyotrophic lateral sclerosis). Life Sci 2000;67:53-9.
44. Chen R, Ende N. The potencial for the use of mononuclear cells from human umbilical cord blood in the treatment of amyotrophic lateral sclerosis. J Med 2000;31:21-30.
45. Willing AE, Garbuzova-Davis S, Saporta S, Mlikem M, Cahill DW, Sanberg PR. hNT neurons delay onset of motor deficits in a model of amyotrophic lateral sclerosis. Brain Res Bull 2001;56:525-30.
46. Garbuzova-Davis S, Willing A, Milliken M, Saporta S, Sowerby B, Cahill DW, et al. Intraspinal implantation of hNT neurons into SOD1 mice with apparent motor deficit. Amyotroph Lateral Scler other Motor Neuron Disord 2001;2:175-180.
47. Garbuzova-Davis S, Willing A, Milliken M, Saporta S, Zigova T, Cahill T, et al. Possitive effect of transplantion of hNT neurons (NTera 2/D1 cell line) in a model of familiar amyotrophic lateral sclerosis. Exp Neurol 2002;174:169-80.
48. Garbuzova-Davis S, Willing AE, Zigova T, Saporta S, Justen EB, et al. Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: distribution, migration, and differentiation. J Hematother Stem Cell Res 2003;12:255-70.
49. Corti F, Locatelli S, Donadoni C, Glugieri M, Papadimitriou D, Strazzer S, et al. Wild-type bone marrow cells ameliorate the phenotype of SOD1-G93A-ALS mice and contribute to CNS, heart, and skeletal muscle tissues. Brain 2004;127:2518-32.
50. Zhao CP, Zhang C, Zhou SN, Xie YM, Wang YH, Huang H, et al. Human mesenchimal stromal cells ameliorate the phenotype of SOD1-G93A ALS mice. Cytotherapy 2007;9:414-26.
51. Corti S, Locatelli F, Papadimitrou D, del Bo R, Nizzardo M, Nardini M, et al. Neural stem cells Lewis X+ CXCR4+ modify disease progression in a amyotrophic lateral sclerosis model. Brain 2007;130:1289-305.
52. Huang H, Zhang C, Zhao CP, Yao XL, Xi J. Effect of transplantation of wild-type bone marrow in moise model of familiar amyotrophic lateral sclerosis. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2006;28:562-6 (abstract).
53. Habisch HJ, Janowski M, Binder D, Kuzma-Kozakiewicz M, Widmann A, Habisch A. Intrathecal application of neuroectodermally eonvered stem cells into a mouse model of ALS: limited intraparenchymal migration and survival narrows therapeutic effects. J Neurol Trasm 2007: DOI 10.1007/s00702-007-0748-y.
54. Xu L, Yan J, Chen D, Welsh AM, Hazel T, Johe K, et al. Human neural stem cell grafts ameliorate motor neuron disease in SOD-1 transgenic rats. Transplantation 2006;82:865-75.
55. Hemmedinger R, Wang J, Malik S, Persinski R, Copeland J, Emerich D, et al. Sertoli cells improve survival of motor neurons in SOD1 transgenic mice, a model of amyotrophic lateral sclerosis. Exp Neurol 2005;196:235-43.
56. Hall PA, Watt FM. Stem cells: the generation and maintenance of cellular diversity. Development 1989;106:619-33.
57. Potten CS, Loeffler M. Stem cells: attributes, cycles, spirals, pitfalls, and uncertainties. Lessons for and from the crypt. Development 1990;110:1001-20.
58. Reynolds BA, Weiss S. Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell. Dev Biol 1996;175:1-13.
59. Martens DJ, Seaberg RM, Van Der Kooy D. In vivo infusions of exogenous growth factors into the fourth ventricle of the adult mouse brain increase the proliferation of neural progenitors around the fourth ventricle and the central canal of the spinal cord. Eur J Neurosci 2002;16:1045-57.
60. Horner PJ, Power AE, Kempermann G, Kuhn HG, Palmer TD, Winkler J, et al. Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord. J Neurosci 2000;20:2218-28.
61. Weiss S, Dunne C, Hewson J, Wohl C, Wheatley M, Peterson AC, et al. Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuraxis. J Neurosci 1996;16:7599-609.
62. Yamamoto S, Yamamoto N, Kitamura T, Nakamura K, Nakafuku M. Proliferation of parenchymal neural progenitors in response to injury in the adult rat spinal cord. Exp Neurol 2001;172:115-27.
63. Laywell ED, Kukekov VJ, Steindler DA. Multipotent neuroespheres can be derived from forebrain subependymal zone and spinal cord of adult miceafter protracted post-mortem intervals. Exp Neurol 1999;156:430-3.
64. García-Verdugo JM, Doetsch F, Wichterle H, Lim DA, Álvarez-Buylla A. Architecture and cell types of the adult subventricularzone: in search of the stem cells. J Neurobiol 1998;36:234-48.
65. Chiasson BJ, Tropepe V, Morshead CM, Van der Kooy D. Adult mammalian forebrain ependymal and subependymal cells demonstrate proliferative potential, but only subependymal cells have neural stem cell characteristics. J Neurosci 1999;19:4462-71.
66. Doetsch F, Caille I, Lim DA, García-Verdugo JM, Álvarez-Buylla A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 1999;97:703-16.
67. Alexanian AR, Crowe MJ, Kurpad SN. Efficient differentiation and integration of lineage-restricted neural precursors in the traumatically injured adult cat spinal cord. J Neurosci Met 2006;150:41-6.
68. McTigue DM, Wei P, Stokes BT. Proliferation of NG2-positive cells and altered oligodendrocyte numbers in the contused rat spinal cord. J Neurosci 2001;21:3392-400.
69. Zai LJ, Wrathall JR Cell proliferation and replacement following contusive spinal cord injury. Glia 2005;50:247-57.
70. Horky LL, Galimi F, Gage FH, Horner PJ. Fate of endogenous stem/progenitor cells following spinal cord injury. J Comp Neurol 2006;498:525-38.
71. Yang H, Lu P, McKay HM, Bernot T, Keirstead H, Steward O, et al. Endogenous neurogenesis replaces oligodendrocytes and astrocytes after primate spinal cord injury. J Neurosci 2006:26:2157-66.
72. Juan L, Dawei Z, Julie AD. Increased number and differentiation of neural precursor cells in the brainstem of superoxide-dismutase 1 (693A-G1H) transgenic mouse model of amyotrophic lateral sclerosis. Neurol Res 2007;29:204-9.
73. Liu Z, Martin LJ. The adult neural stem and progenitor cell niche is altered in amyotrophic lateral sclerosis mouse brain. J Comp Neurol 2006;497:468-88.
74. Mothe AJ, Tator CH. Proliferation, migration and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in adult rat. Neurosci 2005;131:177-87.
75. Takahashi M, Arai K, Kurosawa H, Sueyoshi N, Shirai S. Ependymal cell reactions in spinal cord segments after compression injury in adult rats. J Neuropathol Exp Neurol 2003;62:185-94.
76. Ke Y, Chi L, Xu R, Luo C, Gozal D, Liu R. Early response of endogenous adult neural progenitors cells to acute spinal cord injury in mice. Stem Cells 2006;24:1011-9.
77. Chi L, Ke Y, Luo C, Li B, Gozal D, Kalyanaraman B, et al. Motor neuron degeneration promotes neural progenitor cell proliferation, migration and neurogenesis in the spinal cords of amyotrophic lateral sclerosis mice. Stem Cells 2006;24:34-43.
78. Kojima A, Tator CH. Epidermal growth factor and fibroblast growth factor 2 promotes cause epidermal and functional recovery in spinal cord injury in adult rats. J Neurotrauma 2002;19:223-38.
79. Kojima A, Tator CH. Intratecal administration of epidermal growth factor and fibroblast growth factor 2 cause proliferation of ependimal precursor cells in the adult rat spinal cord in vivo. J Neuropathol Exp Neurol 2000;59:687-97.
80. Otha Y, Nagai M, Nagata T, Murakami T, Pagano I, Nagai H, et al. Intratecal injection of epidermal growth factor and fibroblast growth factor 2 promotes proliferation of neural precursors cells in spinal cord of mice with mutant human SOD1 gene. J Neurosci Res 2006;84:980-92.
81. De Hemptinne I, Boucherie C, Pochet R, Bantubungui K, Schiffmann SN, Maloteaux JM, et al. Unilateral induction of progenitors in the spinal cord of hSOD1(G93A) transgenic rats correlates with asymetrical hind limb paralysis. Neurosci Lett 2006;40:25-9.
82. Michalczyk K, Ziman M. Nestin structure and predicted function in cellular cytoskeletal organisation. Histol Histopathol 2005;20:665-71.
83. Pramatarova A, Laganiere J, Roussel J, Brisebois K, Rouleau GA. Neuron-especific expression of mutant superoxide dismutase 1 in transgenic mice does not lead to motor impairment. J Neurosci 2001;21:3369-74.
84. Lino MM, Scheneider C, Caroni P. Accumulation of SOD1 mutants in postnatal motoneurons does not cause motoneuron pathology or motoneuron disease. J Neurosci 2002;22:4825-32.
85. Miller DW, Cookson M, Dickson DW. Glial cell inclusions and the pathogenesis of neurodegenerative diseases. Neuron Gial Biol 2004;1:13-21.
86. Nelson PT, Soma LA, Lavi E. Microglia in diseases of the central nervous system. Ann Med 2002;34:491-500.
87. Mc Geer PL, Mc Geer EG. Inflammatory processes in amyotrophic lateral sclerosis. Muscl Nerv 2002;26:459-70.
88. Kato S, Hayashi H, Nakashima K, Nambo E, Kato M, Hirano A, et al. Pathological characterization of astrocityc hyaline inclusions in familiar amyotrophic lateral sclerosis. Am J Pathol 1997;151:611-20.
89. Kate S, Takikawa M, Nakashima K, Hirano A, Cleweland DW, Kusaka H, et al. New consensus research on neuropathological aspects of familiar amyotrophic lateral sclerosis with superoxide dismutase 1 (SOD1) gene mutations: inclusions containing SOD1 in neurons and astrocytes. Amyotroph Lateral Scler other Motor Neuron Disord 2000;1:163-679.
90. Jonsson PA, Ernhill K, Andersen PM, Bergemalm D, Brannstrom T, Gredal O, et al. Minute quantities of misfolded mutant superoxide dismutase 1 cause amyotrophic lateral sclerosis. Brain 2004;127:73-88.
91. Brujin LI, Becher MW, Lee MK, Anderson KL, Jenkins NA, Copeland NG, et al. ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progessive disease with SOD1 containing inclusions. Neuron 1997;18:327-38.
92. Brujin LI, Houseweart MK, Kato S, Anderson KL, Anderson SD, Omaha E, et al. Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1. Science 1998;281:1851-4.
93. Stieber A, Gonatas JO, Gonatas NK. Aggregates of mutant protein appear progressively in dendrites, in periaxonal processes of oligodendrocytes, and in neuronal and astrocytic perykarya of mice expressing the SOD1 (G93A) mutation of familiar amyotrophic lateral sclerosis. J Neurol Sci 2000;177:114-23.
94. Rothstein JD, Van Kammen M, Levey AI, Martin U, Kuncl RW. Selective loss glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann Neurol 1995;38:73-84.
95. Howland DS, Liu J, Sche Y, Goad B, Maragakis NJ, Kim B, et al. Focal loss of the glutamate transporter EAAT2 in transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS). Proc Natl Acad Sci USA 2002;99:1604-9.
96. Trotti D, Rolfts A, Danbolt NC, Brown RH, Hedinger MA. SOD1 mutants linked to amyotrophic lateral sclerosis selectively inactivate a glial glutamate transporter. Nat Neuroci 1999;2:427-33.
97. Roy J, Minoti S, Dog L, Figlewiez DA, Durham HD. Glutamate potentiates the toxicity of mutant Cu/Zn-superoxide dismutase in motor neurons by postsynaptic calcium-dependent mechanisms. J Neurosci 1998;18:9673-84.
98. Lu P, Jones LL, Snyder EY, Tuszynski MH. Neural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury. Exp Neurol 2003;181:115-29.
99. Cabanes C, Bonilla S, Tabares L, Martinez S. Neuroprotective effect of adult hematopoietic stem cells in a mouse model of motoneuron degeneration. Neurobiol Dis 2007;26:408-18.
100. Klein SM, Behrstock S, Mc Hugh J, Hoffmann K, Wallace K, Susuki M, et al. GDNF delivery using human neural progenitor cells in a rat model of ALS. Hum Gen Ther 2005;16:509-21.
101. Li L, Wu W, Lin LF, Lei M, Oppenheim RW, Houenou LJ. Rescue of adult mouse motoneurons from injury-induced cell death by glial cell line-derived neurotrophic factor. Proc Natl Acad Sci USA 1995;92:9771-5.
102. Kaspar BK, Llado J, Sherkat N, Rothstein JD, Gage FH. Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS model. Science 2003;301:839-42.
103. Gorio A, Lesma E, Madashi L, Di Giulio AM. Co-administration of IGF-1 and glycosaminogycans greatly delays motor neuron disease and affects expresion in the wobbler mouse: a long term study. J Neurochem 2002;12:193-202.
104. Zheng C, Nennesmo I, Fadeel B, Henter JL. Vascular endothelial growth factor prolongs survival in a transgenic mouse model of ALS. Ann Neurol 2004;56:564-7.
105. Azzouz M, Ralph GS, Storkebaum E, Walmsley LE, Mitrophanous KA, Kingsman SM, et al. VEGF delivery with retrogradely transported lentivector prolongs survival in a mouse ALS model. Nature 2004;429:413-7.
106. Jin K, Zhu Y, Sun Y, Mao XO, Xie L, Greensberg DA. Vascular endothelial gouwth factor (VEGF) stimulates in vitro and in vivo. Proc Natl Acad Sci USA 2002;99:11946-50.
107. Sun W, Funakoshi H, Nakamura T. Overexpression of HGF retards disease progression and prolongs life span in a transgenic mouse model of ALS. J Neurosci 2002;22:6537-48.
108. Mitsumoto H, Klinkosz B, Pioro EP, Tsuzaka K, Ishiyama T, O'Leary RM, et al. Effects of cardiotrophin-1 (CT-1) in a mouse motor neuron disease. Muscl Nerv 2001;24:769-77.
109. Feeney SJ, Austin L, Bennett TM, Kurek JB, Jean François MJ, Muldoon C, et al. The effect of leukaemia inhibitory factor on SOD1 G93A murine amyotrophic lateral sclerosis. Cytokine 2003;23:108-18.
110. Azari MF, Lopes EC, Stubna C, Turner BJ, Zhang D, Nicola NA, et al. Behavioural and anatomical effects of systemically administered leukaemia inhibitory factor in the SOD1 (G93A GIH) mouse model of familiar amyotrophic lateral sclerosis. Brain Res 2003;982:92-7.
111. MIR R, Chen W, Höke A. Pleiotrophin is a neurotrophic factor for spinal motor neurons. Proc Natl Acad Sci USA 2002;104:4664-9.
112. Suzuki M, McHugh J, Tork C, Seller B, Klein SM, Aebisher P, et al. GDFN secreting human neural progenitor cells protect dying motor neurons, but not their projection to muscle in a rat model of familiar ALS. Plos One 2007: Doi 10.1371/0000689.
113. Zhao CP, Zang C, Wang YH, Zhou SN, Zhou C, Li WY, et al. Signals in pathological CNS extracts of ALS mice promote hMSC neurogenic differentiation in vitro. Cell Biol Int 2007.
114. Yan J, Xu L, Welsh AM, Chen D, Hazhel T, Johe K, et al. Combined inmunosupressive agents or CD4 antibodies prolong survival of human neural stem cells graft and improve disease outcomes in amyotrophic lateral sclerosis transgenic mice. Stem Cells 2006;24:1976-85.
115. Fujiwara I, Tanaka N, Ishida O, Fujimoto Y, Marakami T, Kahihara H, et al. Intravenously injected neural progenitor cells of transgenic rats can migrate of the injured spinal cord and differenciate into neurons, astrocytes and oligodendrocytes. Neurosci Lett 2004;366:287-91.
116. Ohta M, Suzuki Y, Noda T, Kataoka M, Chou H, Ishikawa N, et al. Implantation of neural stem cells via cerebrospinal fluid into the injured root. Neuroreport 2004;15:1249-53.
117. Bakshi A, Hunter C, Swanger S, Lepore A, Fisher I. Minimally invasive delivery of stem cells for spinal cord injury: advantages of lumbar puncture technique. J Neurosurg Spine 2004;1:330-7.
118. Bakshi A, Barshinger AL, Swanger S, Madhavani V, Shumsky JS, Neuhuber B, et al. Lumbar puncture delivery of bone marrow stromal cells in spinal cord contusion: a novel method for minimally invasive stem cell transplantation. J Neurotrauma 2006:23:55-65.
119. Lepore A, Bakshi A, Swanger S, Rao MS, Fisher I. Neural precursor cells can be delivered into the injured cervical spinal cord by intrathecal injection at the lumbar cord. Brain Res 2005;1045:206-16.
120. Wu S, Suzuki S, Kitada M, Katoaka K, Kitaura M, Chou H, et al. New method for transplantation of neurosphere cells into injured spinal cord through cerebrospinal fluid in rat. Neurosci Lett 2002;318:81-4.
121. Bai H, Suzuki Y, Nota T, Wu S, Kataoka K, Kitada M, et al. Dissemination and proliferation of neural stem cells on the spinal cord by injection into the fourth ventricle of the rat: a method for cell transplantation. J Neurosci Meth 2003;124:181-7.
122. Ohta M, Suzuki Y, Noda T, Ejiri Y, Dezawa M, Kataoka M, et al. Bone marrow stromal cells injured into the cerebrospinal fluid promote functional recovery of the injured rat spinal cord with reduced cavity formation. Exp Neurol 2004;187:266-78.
123. Dasari VR, Spomar DG, Li L, Gujrati M, Rao JS, Dinh DH. Umbilical cord blood stem cell mediated downregulation of fas improves functional recovery of rats after spinal cord injury. Neurochem Res 2007:
124. Parr AM, Kultbaski I, Tator CH. Trasplantation of adult rat spinal cord stem/progenitor cell for spinal cord injury. J Neurotrauma 2007;24:835-45.
125. Garbuzova-Davis S, Willing A, Saporta S, Justen EB, Misiuta IE, Dellis J, et al. Multiple transplants of hNT cells into spinal cord of SOD1 mouse model of familiar amyotrophic lateral sclerosis. Amyotroph Lateral Scler other Motor Neuron Disord 2006;7:221-6.
126. Grieb P. Transgenic models of amyotrophic lateral sclerosis. Folia Neuropathol 2004;42:239-48.
127. Wood MJ, Sloan DJ, Wood KJ, Charlton HM. Indefinite survival of neural xenografts induced with anti-CD4 monoclonal antibodies. Neuroscience 1996;76:775-89.
128. Li P, Tessler A, Hass SS, Fischer I, Rao MS, Sezler ME. Fate of immortalized human neuronal progenitor cells transplanted in rat spinal cord. Arch Neurol 2005;62:223-9.
129. Karlsson J, Fong KS, Hansson MJ, Elmer E, Csiszar K, Keep MF. Life span extension and reduced neuronal death after weekly intraventricular ciclosporin injections in the G93A transgenic mouse model of amyotrophic lateral sclerosis. J Neurosurg 2004;101:128-37.
130. Anneser JM, Gmerek A, Gerkrath J, Borasio GD, Heumann R. Inmunosuppressant FK506 does not exert beneficial effects in symptomatic G93A superoxide dismutase 1 transgenic mice. Neuroreport 2001;12:2663-5.
131. Hendriks WA, Pak ES, Owensby JP, Menta KJ, Glazova M, Moretto J, et al. Predifferenciated embryonic stem cells prevent chronic pain behaviours and restory function following spinal cord injury in mice. Mol Med 2006;12:34-46.
132. Giordano A, Galderisi U, Marino IR. From the laboratory bench to the patients's bedside: an update of clinical trials with mesenchymal stem cells. J Cell Physiol 2007;211:27-35.