The multiple aspects of stroke and stem cell therapy

Current Molecular Medicine

Volumn 13, Issue 5, 2013, Pages 821-831

  Onteniente, B ^a  

^a I Stem   (France)

Author keywords

Cell replacement therapy; Cerebral ischemia; Intracerebral transplantation; Neuroprotection; Neurovascular diseases; Regenerative medicine

Indexed keywords

BASIC FIBROBLAST GROWTH FACTOR RECEPTOR; CHEMOKINE RECEPTOR CXCR4; CHORIONIC GONADOTROPIN; CILIARY NEUROTROPHIC FACTOR; CYCLOSPORIN A; EPIDERMAL GROWTH FACTOR; ERYTHROPOIETIN; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; GRANULOCYTE COLONY STIMULATING FACTOR; HYPOXIA INDUCIBLE FACTOR 1ALPHA; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 8; NERVE GROWTH FACTOR; NEUROTROPHIN 3; NTX 265; SOMATOMEDIN C; STROMAL CELL DERIVED FACTOR 1ALPHA; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VASCULOTROPIN;

ARTICLE; BRAIN ISCHEMIA; CELL DIFFERENTIATION; CELL MIGRATION; CELL PROLIFERATION; CEREBROVASCULAR ACCIDENT; HIPPOCAMPUS POTENTIAL; HUMAN; MESENCHYMAL STEM CELL; NERVE CELL PLASTICITY; NERVOUS SYSTEM DEVELOPMENT; NEURAL STEM CELL TRANSPLANTATION; NEUROPROTECTION; NONHUMAN; PARACRINE SIGNALING; PARKINSON DISEASE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC);

ANIMALS; BRAIN INFARCTION; BRAIN ISCHEMIA; CELL MOVEMENT; CELL PROLIFERATION; EMBRYONIC STEM CELLS; HISTOCOMPATIBILITY; HUMANS; INDUCED PLURIPOTENT STEM CELLS; NEUROGENESIS; STEM CELL TRANSPLANTATION;

EID: 84881326575     PISSN: 15665240     EISSN: 18755666     Source Type: Journal    
DOI: 10.2174/1566524011313050013     Document Type: Article

References (170)

1. Hassan A, Markus HS. Genetics and ischaemic stroke. Brain 2000; 123 (Pt 9): 1784-1812.
2. Rubattu S, Giliberti R, Volpe M. Etiology and pathophysiology of stroke as a complex trait. Am J Hypertens 2000; 13: 1139-1148.
3. Natowicz M, Kelley RI. Mendelian etiologies of stroke. Ann Neurol 1987; 22: 175-192.
4. Ballabio E, Bersano A, Bresolin N, Candelise L. Monogenic vessel diseases related to ischemic stroke: a clinical approach. J Cereb Blood Flow Metab 2007; 27: 1649-1662.
5. Pantoni L, Gorelick P. Advances in vascular cognitive impairment 2010. Stroke 2011; 42: 291-293.
6. Kleindorfer D, Xu Y, Moomaw CJ, et al. US geographic distribution of rt-PA utilization by hospital for acute ischemic stroke. Stroke 2009; 40: 3580-3584.
7. Koch P, Kokaia Z, Lindvall O, Brustle O. Emerging concepts in neural stem cell research: autologous repair and cell-based disease modelling. Lancet Neurol 2009; 8: 819-829.
8. Bjorklund A, Dunnett SB, Brundin P, et al. Neural transplantation for the treatment of Parkinson's disease. Lancet Neurol 2003; 2: 437-445.
9. Bliss TM, Andres RH, Steinberg GK. Optimizing the success of cell transplantation therapy for stroke. Neurobiol Dis 2010; 37: 275-283.
10. Burns TC, Verfaillie CM, Low WC. Stem cells for ischemic brain injury: a critical review. J Comp Neurol 2009; 515: 125-144.
11. Chopp M, Steinberg GK, Kondziolka D, et al. Who's in favor of translational cell therapy for stroke: STEPS forward please? Cell Transplant 2009; 18: 691-693.
12. Onteniente B, Polentes J. Regenerative Medicine for Stroke - Are We There Yet? Cerebrovasc Dis 2011; 31: 544-551.
13. Brustle O, McKay RD. Neuronal progenitors as tools for cell replacement in the nervous system. Curr Opin Neurobiol 1996; 6: 688-695.
14. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997; 276: 71-74.
15. Verfaillie CM. Multipotent adult progenitor cells: an update. Novartis Found Symp 2005; 265: 55-61; discussion 61-55, 92-57.
16. Alvarez-Buylla A, Kohwi M, Nguyen TM, Merkle FT. The heterogeneity of adult neural stem cells and the emerging complexity of their niche. Cold Spring Harb Symp Quant Biol 2008; 73: 357-365.
17. Doetsch F, Caille I, Lim DA, et al. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 1999; 97: 703-716.
18. Lim DA, Tramontin AD, Trevejo JM, et al. Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 2000; 28: 713-726.
19. Shen Q, Goderie SK, Jin L, et al. Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science 2004; 304: 1338-1340.
20. Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 1992; 255: 1707-1710.
21. Chatelin S, Sol J, Jozan S, et al. Multipotent neural stem cells from the adult human brain: a potential tool for brain self repair. Acta Neurochirurgica 2006; 148: 3-4.
22. Conti L, Pollard SM, Gorba T, et al. Niche-independent symmetrical self-renewal of a mammalian tissue stem cell. PLoS Biol 2005; 3: e283.
23. Gore A, Li Z, Fung HL, et al. Somatic coding mutations in human induced pluripotent stem cells. Nature 2011; 471: 63-67.
24. Hussein SM, Batada NN, Vuoristo S, et al. Copy number variation and selection during reprogramming to pluripotency. Nature 2011; 471: 58-62.
25. Lefort N, Perrier AL, Laabi Y, et al. Human embryonic stem cells and genomic instability. Regen Med 2009; 4: 899-909.
26. Lu B, Malcuit C, Wang S, et al. Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration. Stem Cells 2009; 27: 2126-2135.
27. Coporation G. World's first clinical trial of human embryonic stem cell therapy cleared. Regen Med 2009; 4: 161.
28. Thomas RJ, Hope AD, Hourd P, et al. Automated, serum-free production of CTX0E03: a therapeutic clinical grade human neural stem cell line. Biotechnol Lett 2009; 31: 1167-1172.
29. Cheung WM, Fu WY, Hui WS, Ip NY. Production of human CNS neurons from embryonal carcinoma cells using a cell aggregation method. Biotechniques 1999; 26: 946-948, 950-952, 954.
30. Kondziolka D, Wechsler L, Tyler-Kabara E, Achim C. The role of cell therapy for stroke. Neurosurg Focus 2002; 13: e1.
31. Kondziolka D, Steinberg GK, Wechsler L, et al. Neurotransplantation for patients with subcortical motor stroke: a phase 2 randomized trial. J Neurosurg 2005; 103: 38-45.
32. Detante O, Moisan A, Dimastromatteo J, et al. Intravenous administration of 99mTc-HMPAO-labeled human mesenchymal stem cells after stroke: in vivo imaging and biodistribution. Cell Transplant 2009; 18: 1369-1379.
33. Bang OY, Lee JS, Lee PH, Lee G. Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 2005; 57: 874-882.
34. Seminatore C, Polentes J, Ellman D, et al. The postischemic environment differentially impacts teratoma or tumor formation after transplantation of human embryonic stem cell-derived neural progenitors. Stroke 2010; 41: 153-159.
35. Ying QL, Stavridis M, Griffiths D, et al. Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture. Nat Biotechnol 2003; 21: 183-186.
36. 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.
37. Weiss S, Dunne C, Hewson J, et al. Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis. J Neurosci 1996; 16: 7599-7609.
38. Flax JD, Aurora S, Yang C, et al. Engraftable human neural stem cells respond to developmental cues, replace neurons, and express foreign genes. Nat Biotechnol 1998; 16: 1033-1039.
39. Kim D, Chun BG, Kim YK, et al. In vivo tracking of human mesenchymal stem cells in experimental stroke. Cell Transplant 2008; 16: 1007-1012.
40. Daadi MM, Maag AL, Steinberg GK. Adherent self-renewable human embryonic stem cell-derived neural stem cell line: functional engraftment in experimental stroke model. PLoS One 2008; 3: e1644.
41. Bain G, Kitchens D, Yao M, et al. Embryonic stem cells express neuronal properties in vitro. Dev Biol 1995; 168: 342-357.
42. Bibel M, Richter J, Schrenk K, et al. Differentiation of mouse embryonic stem cells into a defined neuronal lineage. Nat Neurosci 2004; 7: 1003-1009.
43. Zhang SC, Wernig M, Duncan ID, et al. In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat Biotechnol 2001; 19: 1129-1133.
44. Chambers SM, Fasano CA, Papapetrou EP, et al. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 2009; 27: 275-280.
45. Anderson L, Burnstein RM, He X, et al. Gene expression changes in long term expanded human neural progenitor cells passaged by chopping lead to loss of neurogenic potential in vivo. Exp Neurol 2007; 204: 512-524.
46. Cesnulevicius K, Timmer M, Wesemann M, et al. Nucleofection is the most efficient nonviral transfection method for neuronal stem cells derived from ventral mesencephali with no changes in cell composition or dopaminergic fate. Stem Cells 2006; 24: 2776-2791.
47. Kim HJ, Sugimori M, Nakafuku M, Svendsen CN. Control of neurogenesis and tyrosine hydroxylase expression in neural progenitor cells through bHLH proteins and Nurr1. Exp Neurol 2007; 203: 394-405.
48. Spiliotopoulos D, Goffredo D, Conti L, et al. An optimized experimental strategy for efficient conversion of embryonic stem (ES)-derived mouse neural stem (NS) cells into a nearly homogeneous mature neuronal population. Neurobiol Dis 2009; 34: 320-331.
49. Defontaines B, Peschanski M, Onteniente B. Host dopaminergic afferents affect the development of DARPP-32 immunoreactivity in transplanted embryonic striatal neurons. Neuroscience 1992; 48: 857-869.
50. Erdo F, Buhrle C, Blunk J, et al. Host-dependent tumorigenesis of embryonic stem cell transplantation in experimental stroke. J Cereb Blood Flow Metab 2003; 23: 780-785.
51. Hicks AU, Lappalainen RS, Narkilahti S, et al. Transplantation of human embryonic stem cell-derived neural precursor cells and enriched environment after cortical stroke in rats: cell survival and functional recovery. Eur J Neurosci 2009; 29: 562-574.
52. Chen J, Zhang ZG, Li Y, et al. Intravenous administration of human bone marrow stromal cells induces angiogenesis in the ischemic boundary zone after stroke in rats. Circ Res 2003; 92: 692-699.
53. Taguchi A, Soma T, Tanaka H, et al. Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J Clin Invest 2004; 114: 330-338.
54. Wei L, Keogh CL, Whitaker VR, et al. Angiogenesis and stem cell transplantation as potential treatments of cerebral ischemic stroke. Pathophysiology 2005; 12: 47-62.
55. Saver JL. Time is brain--quantified. Stroke 2006; 37: 263-266.
56. Benchoua A, Guegan C, Couriaud C, et al. Specific caspase pathways are activated in the two stages of cerebral infarction. J Neurosci 2001; 21: 7127-7134.
57. Mueller FJ, McKercher SR, Imitola J, et al. At the interface of the immune system and the nervous system: how neuroinflammation modulates the fate of neural progenitors in vivo. Ernst Schering Res Found Workshop 2005; 83-114.
58. Hill WD, Hess DC, Martin-Studdard A, et al. SDF-1 (CXCL12) is upregulated in the ischemic penumbra following stroke: association with bone marrow cell homing to injury. J Neuropathol Exp Neurol 2004; 63: 84-96.
59. Robin AM, Zhang ZG, Wang L, et al. Stromal cell-derived factor 1alpha mediates neural progenitor cell motility after focal cerebral ischemia. J Cereb Blood Flow Metab 2006; 26: 125-134.
60. Lambertsen KL, Clausen BH, Babcock AA, et al. Microglia protect neurons against ischemia by synthesis of tumor necrosis factor. J Neurosci 2009; 29: 1319-1330.
61. Gonzalez-Perez O, Jauregui-Huerta F, Galvez-Contreras AY. Immune system modulates the function of adult neural stem cells. Curr Immunol Rev 2010; 6: 167-173.
62. Lo EH, Dalkara T, Moskowitz MA. Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci 2003; 4: 399-415.
63. Zhao BQ, Tejima E, Lo EH. Neurovascular proteases in brain injury, hemorrhage and remodeling after stroke. Stroke 2007; 38: 748-752.
64. Lanfranconi S, Locatelli F, Corti S, et al. Growth factors in ischemic stroke. J Cell Mol Med 2011; 15: 1645-1687.
65. Wakabayashi K, Nagai A, Sheikh AM, et al. Transplantation of human mesenchymal stem cells promotes functional improvement and increased expression of neurotrophic factors in a rat focal cerebral ischemia model. J Neurosci Res 2010; 88: 1017-1025.
66. De Palma C, Falcone S, Panzeri C, et al. Endothelial nitric oxide synthase overexpression by neuronal cells in neurodegeneration: a link between inflammation and neuroprotection. J Neurochem 2008; 106: 193-204.
67. Wada T, Haigh JJ, Ema M, et al. Vascular endothelial growth factor directly inhibits primitive neural stem cell survival but promotes definitive neural stem cell survival. J Neurosci 2006; 26: 6803-6812.
68. Issa R, AlQteishat A, Mitsios N, et al. Expression of basic fibroblast growth factor mRNA and protein in the human brain following ischaemic stroke. Angiogenesis 2005; 8: 53-62.
69. Rickhag M, Teilum M, Wieloch T. Rapid and long-term induction of effector immediate early genes (BDNF, Neuritin and Arc) in peri-infarct cortex and dentate gyrus after ischemic injury in rat brain. Brain Res 2007; 1151: 203-210.
70. Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 2007; 10: 1387-1394.
71. Galli R, Pagano SF, Gritti A, Vescovi AL. Regulation of neuronal differentiation in human CNS stem cell progeny by leukemia inhibitory factor. Dev Neurosci 2000; 22: 86-95.
72. Bresjanac M, Antauer G. Reactive astrocytes of the quinolinic acid-lesioned rat striatum express GFRalpha1 as well as GDNF in vivo. Exp Neurol 2000; 164: 53-59.
73. Asada H, Ip NY, Pan L, et al. Time course of ciliary neurotrophic factor mRNA expression is coincident with the presence of protoplasmic astrocytes in traumatized rat striatum. J Neurosci Res 1995; 40: 22-30.
74. Song H, Stevens CF, Gage FH. Astroglia induce neurogenesis from adult neural stem cells. Nature 2002; 417: 39-44.
75. Neumann J, Sauerzweig S, Ronicke R, et al. Microglia cells protect neurons by direct engulfment of invading neutrophil granulocytes: a new mechanism of CNS immune privilege. J Neurosci 2008; 28: 5965-5975.
76. Barone FC, Hillegass LM, Price WJ, et al. Polymorphonuclear leukocyte infiltration into cerebral focal ischemic tissue: myeloperoxidase activity assay and histologic verification. J Neurosci Res 1991; 29: 336-345.
77. Ekdahl CT, Kokaia Z, Lindvall O. Brain inflammation and adult neurogenesis: the dual role of microglia. Neuroscience 2009; 158: 1021-1029.
78. Darsalia V, Allison SJ, Cusulin C, et al. Cell number and timing of transplantation determine survival of human neural stem cell grafts in stroke-damaged rat brain. J Cereb Blood Flow Metab 2011; 31: 235-242.
79. Altman J, James AE. Ulcer in a Meckel's diverticulum demonstrated radiographically. Br J Radiol 1970; 43: 816-817.
80. Deierborg T, Roybon L, Inacio AR, et al. Brain injury activates microglia that induce neural stem cell proliferation ex vivo and promote differentiation of neurosphere-derived cells into neurons and oligodendrocytes. Neuroscience 2010; 171: 1386-1396.
81. Rafalski VA, Brunet A. Energy metabolism in adult neural stem cell fate. Prog Neurobiol 2011; 93: 182-203.
82. Kouroupi G, Lavdas AA, Gaitanou M, et al. Lentivirus-mediated expression of insulin-like growth factor-I promotes neural stem/precursor cell proliferation and enhances their potential to generate neurons. J Neurochem 2010; 115: 460-474.
83. Katakowski M, Chen J, Zhang ZG, et al. Stroke-induced subventricular zone proliferation is promoted by tumor necrosis factor-alpha-converting enzyme protease activity. J Cereb Blood Flow Metab 2007; 27: 669-678.
84. Kokaia Z, Lindvall O. Neurogenesis after ischaemic brain insults. Curr Opin Neurobiol 2003; 13: 127-132.
85. Goings GE, Sahni V, Szele FG. Migration patterns of subventricular zone cells in adult mice change after cerebral cortex injury. Brain Res 2004; 996: 213-226.
86. Kokovay E, Goderie S, Wang Y, et al. Adult SVZ lineage cells home to and leave the vascular niche via differential responses to SDF1/CXCR4 signaling. Cell Stem Cell 2010; 7: 163-173.
87. Belmadani A, Tran PB, Ren D, Miller RJ. Chemokines regulate the migration of neural progenitors to sites of neuroinflammation. J Neurosci 2006; 26: 3182-3191.
88. Imitola J, Raddassi K, Park KI, et al. Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci USA 2004; 101: 18117-18122.
89. Thored P, Heldmann U, Gomes-Leal W, et al. Long-term accumulation of microglia with proneurogenic phenotype concomitant with persistent neurogenesis in adult subventricular zone after stroke. Glia 2009; 57: 835-849.
90. Zhang ZG, Zhang L, Tsang W, et al. Correlation of VEGF and angiopoietin expression with disruption of blood-brain barrier and angiogenesis after focal cerebral ischemia. J Cereb Blood Flow Metab 2002; 22: 379-392.
91. Tran PB, Ren D, Veldhouse TJ, Miller RJ. Chemokine receptors are expressed widely by embryonic and adult neural progenitor cells. J Neurosci Res 2004; 76: 20-34.
92. Wiltrout C, Lang B, Yan Y, et al. Repairing brain after stroke: a review on post-ischemic neurogenesis. Neurochem Int 2007; 50: 1028-1041.
93. Ohab JJ, Fleming S, Blesch A, Carmichael ST. A neurovascular niche for neurogenesis after stroke. J Neurosci 2006; 26: 13007-13016.
94. Cunningham LA, Wetzel M, Rosenberg GA. Multiple roles for MMPs and TIMPs in cerebral ischemia. Glia 2005; 50: 329-339.
95. Belvindrah R, Hankel S, Walker J, et al. Beta1 integrins control the formation of cell chains in the adult rostral migratory stream. J Neurosci 2007; 27: 2704-2717.
96. Janowski M, Lukomska B, Domanska-Janik K. Migratory capabilities of human umbilical cord blood-derived neural stem cells (HUCB-NSC) in vitro. Acta Neurobiol Exp (Wars) 2011; 71: 24-35.
97. Aubry L, Bugi A, Lefort N, et al. Striatal progenitors derived from human ES cells mature into DARPP32 neurons in vitro and in quinolinic acid-lesioned rats. Proc Natl Acad Sci USA 2008; 105: 16707-16712.
98. Dihne M, Bernreuther C, Hagel C, et al. Embryonic stem cell-derived neuronally committed precursor cells with reduced teratoma formation after transplantation into the lesioned adult mouse brain. Stem Cells 2006; 24: 1458-1466.
99. Joannides AJ, Webber DJ, Raineteau O, et al. Environmental signals regulate lineage choice and temporal maturation of neural stem cells from human embryonic stem cells. Brain 2007; 130: 1263-1275.
100. Suhonen JO, Peterson DA, Ray J, Gage FH. Differentiation of adult hippocampus-derived progenitors into olfactory neurons in vivo. Nature 1996; 383: 624-627.
101. Nishida A, Takahashi M, Tanihara H, et al. Incorporation and differentiation of hippocampus-derived neural stem cells transplanted in injured adult rat retina. Invest Ophthalmol Vis Sci 2000; 41: 4268-4274.
102. Young MJ, Ray J, Whiteley SJ, et al. Neuronal differentiation and morphological integration of hippocampal progenitor cells transplanted to the retina of immature and mature dystrophic rats. Mol Cell Neurosci 2000; 16: 197-205.
103. Grigoriadis N, Lourbopoulos A, Lagoudaki R, et al. Variable behavior and complications of autologous bone marrow mesenchymal stem cells transplanted in experimental autoimmune encephalomyelitis. Exp Neurol 2011; 230: 78-89.
104. Billingham RE, Boswell T. Studies on the problem of corneal homografts. Proc R Soc Lond B Biol Sci 1953; 141: 392-406.
105. Barker RA, Widner H. Immune problems in central nervous system cell therapy. NeuroRx 2004; 1: 472-481.
106. Poltorak M, Freed WJ. Immunological reactions induced by intracerebral transplantation: evidence that host microglia but not astroglia are the antigen-presenting cells. Exp Neurol 1989; 103: 222-233.
107. Pan Y, Nastav JB, Zhang H, et al. Engraftment of freshly isolated or cultured human umbilical cord blood cells and the effect of cyclosporin A on the outcome. Exp Neurol 2005; 192: 365-372.
108. Freeman TB, Olanow CW, Hauser RA, et al. Bilateral fetal nigral transplantation into the postcommissural putamen in Parkinson's disease. Ann Neurol 1995; 38: 379-388.
109. Robichon R, Jaafar A, Terqui M, et al. Pig xenografts to the immunocompetent rat brain: Survival rates using distinct neurotoxic lesions in the nigrostriatal pathway and two rat strains. Exp Neurol 2005; 194: 333-340.
110. Wennersten A, Holmin S, Al Nimer F, et al. Sustained survival of xenografted human neural stem/progenitor cells in experimental brain trauma despite discontinuation of immunosuppression. Exp Neurol 2006; 199: 339-347.
111. Duan WM, Widner H, Cameron RM, Brundin P. Quinolinic acid-induced inflammation in the striatum does not impair the survival of neural allografts in the rat. Eur J Neurosci 1998; 10: 2595-2606.
112. Bachoud-Levi AC, Maison P, Bartolomeo P, et al. Retest effects and cognitive decline in longitudinal follow-up of patients with early HD. Neurology 2001; 56: 1052-1058.
113. Kordower JH, Styren S, Clarke M, et al. Fetal grafting for Parkinson's disease: expression of immune markers in two patients with functional fetal nigral implants. Cell Transplant 1997; 6: 213-219.
114. Freeman TB, Cicchetti F, Bachoud-Levi AC, Dunnett SB. Technical factors that influence neural transplant safety in Huntington's disease. Exp Neurol 2011; 227: 1-9.
115. Krystkowiak P, Gaura V, Labalette M, et al. Alloimmunisation to donor antigens and immune rejection following foetal neural grafts to the brain in patients with Huntington's disease. PLoS One 2007; 2: e166.
116. Savitz SI, Dinsmore J, Wu J, et al. Neurotransplantation of fetal porcine cells in patients with basal ganglia infarcts: a preliminary safety and feasibility study. Cerebrovasc Dis 2005; 20: 101-107.
117. Leveque X, Cozzi E, Naveilhan P, Neveu I. Intracerebral xenotransplantation: recent findings and perspectives for local immunosuppression. Curr Opin Organ Transplant 2011; 16: 190-194.
118. Martin C, Plat M, Nerriere-Daguin V, et al. Transgenic expression of CTLA4-Ig by fetal pig neurons for xenotransplantation. Transgenic Res 2005; 14: 373-384.
119. Deacon TW, Pakzaban P, Burns LH, et al. Cytoarchitectonic development, axon-glia relationships, and long distance axon growth of porcine striatal xenografts in rats. Exp Neurol 1994; 130: 151-167.
120. Freed CR, Greene PE, Breeze RE, et al. Transplantation of embryonic dopamine neurons for severe Parkinson's disease. N Engl J Med 2001; 344: 710-719.
121. Nelson PT, Kondziolka D, Wechsler L, et al. Clonal human (hNT) neuron grafts for stroke therapy: neuropathology in a patient 27 months after implantation. Am J Pathol 2002; 160: 1201-1206.
122. Klehmet J, Harms H, Richter M, et al. Stroke-induced immunodepression and post-stroke infections: lessons from the preventive antibacterial therapy in stroke trial. Neuroscience 2009; 158: 1184-1193.
123. Li L, Jiang Q, Ding G, et al. Effects of administration route on migration and distribution of neural progenitor cells transplanted into rats with focal cerebral ischemia, an MRI study. J Cereb Blood Flow Metab 2010; 30: 653-662.
124. Michel-Monigadon D, Bonnamain V, Nerriere-Daguin V, et al. Trophic and immunoregulatory properties of neural precursor cells: Benefit for intracerebral transplantation. Exp Neurol 2011; 230: 35-47.
125. Chen JR, Cheng GY, Sheu CC, et al. Transplanted bone marrow stromal cells migrate, differentiate and improve motor function in rats with experimentally induced cerebral stroke. J Anat 2008; 213: 249-258.
126. Chu K, Kim M, Park KI, et al. Human neural stem cells improve sensorimotor deficits in the adult rat brain with experimental focal ischemia. Brain Res 2004; 1016: 145-153.
127. Mochizuki N, Takagi N, Kurokawa K, et al. Injection of neural progenitor cells improved learning and memory dysfunction after cerebral ischemia. Exp Neurol 2008; 211: 194-202.
128. Skardelly M, Gaber K, Burdack S, et al. Long-term benefit of human fetal neuronal progenitor cell transplantation in a clinically adapted model after traumatic brain injury. J Neurotrauma 2011; 28: 401-414.
129. Li Y, Chen J, Chen XG, et al. Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional recovery. Neurology 2002; 59: 514-523.
130. Lee ST, Chu K, Jung KH, et al. Anti-inflammatory mechanism of intravascular neural stem cell transplantation in haemorrhagic stroke. Brain 2008; 131: 616-629.
131. Liu YP, Seckin H, Izci Y, et al. Neuroprotective effects of mesenchymal stem cells derived from human embryonic stem cells in transient focal cerebral ischemia in rats. J Cereb Blood Flow Metab 2009; 29: 780-791.
132. Bacigaluppi M, Pluchino S, Peruzzotti-Jametti L, et al. Delayed post-ischaemic neuroprotection following systemic neural stem cell transplantation involves multiple mechanisms. Brain 2009; 132: 2239-2251.
133. Li Y, Chopp M, Chen J, et al. Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice. J Cereb Blood Flow Metab 2000; 20: 1311-1319.
134. Bao X, Wei J, Feng M, et al. Transplantation of human bone marrow-derived mesenchymal stem cells promotes behavioral recovery and endogenous neurogenesis after cerebral ischemia in rats. Brain Res 2011; 1367: 103-113.
135. Madhavan L, Ourednik V, Ourednik J. Neural stem/progenitor cells initiate the formation of cellular networks that provide neuroprotection by growth factor-modulated antioxidant expression. Stem Cells 2008; 26: 254-265.
136. Lee HJ, Lim IJ, Lee MC, Kim SU. Human neural stem cells genetically modified to overexpress brain-derived neurotrophic factor promote functional recovery and neuroprotection in a mouse stroke model. J Neurosci Res 2010; 88: 3282-3294.
137. Chopp M, Li Y, Zhang ZG. Mechanisms underlying improved recovery of neurological function after stroke in the rodent after treatment with neurorestorative cell-based therapies. Stroke 2009; 40: S143-145.
138. Locatelli F, Bersano A, Ballabio E, et al. Stem cell therapy in stroke. Cell Mol Life Sci 2009; 66: 757-772.
139. Stroemer P, Patel S, Hope A, et al. The neural stem cell line CTX0E03 promotes behavioral recovery and endogenous neurogenesis after experimental stroke in a dose-dependent fashion. Neurorehabil Neural Repair 2009; 23: 895-909.
140. Ramos-Cabrer P, Justicia C, Wiedermann D, Hoehn M. Stem cell mediation of functional recovery after stroke in the rat. PLoS One 2010; 5: e12779.
141. Horie N, Pereira MP, Niizuma K, et al. Transplanted Stem Cell-Secreted VEGF Effects Post-Stroke Recovery, Inflammation, and Vascular Repair. Stem Cells 2011; (Epub ahead of print).
142. Bakondi B, Shimada IS, Perry A, et al. CD133 identifies a human bone marrow stem/progenitor cell sub-population with a repertoire of secreted factors that protect against stroke. Mol Ther 2009; 17: 1938-1947.
143. Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem 2006; 98: 1076-1084.
144. Buhnemann C, Scholz A, Bernreuther C, et al. Neuronal differentiation of transplanted embryonic stem cell-derived precursors in stroke lesions of adult rats. Brain 2006; 129: 3238-3248.
145. Jeltsch H, Yee J, Aloy E, et al. Transplantation of neurospheres after granule cell lesions in rats: cognitive improvements despite no long-term immunodetection of grafted cells. Behav Brain Res 2003; 143: 177-191.
146. 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: 115-129.
147. Liu Z, Zhang RL, Li Y, et al. Remodeling of the corticospinal innervation and spontaneous behavioral recovery after ischemic stroke in adult mice. Stroke 2009; 40: 2546-2551.
148. Liu Z, Li Y, Zhang ZG, et al. Bone marrow stromal cells enhance inter- and intracortical axonal connections after ischemic stroke in adult rats. J Cereb Blood Flow Metab 2010; 30: 1288-1295.
149. Jiang Q, Zhang ZG, Ding GL, et al. MRI detects white matter reorganization after neural progenitor cell treatment of stroke. Neuroimage 2006; 32: 1080-1089.
150. Shen LH, Li Y, Gao Q, et al. Down-regulation of neurocan expression in reactive astrocytes promotes axonal regeneration and facilitates the neurorestorative effects of bone marrow stromal cells in the ischemic rat brain. Glia 2008; 56: 1747-1754.
151. Piccini P, Brooks DJ, Bjorklund A, et al. Dopamine release from nigral transplants visualized in vivo in a Parkinson's patient. Nat Neurosci 1999; 2: 1137-1140.
152. Meltzer CC, Kondziolka D, Villemagne VL, et al. Serial [18F] fluorodeoxyglucose positron emission tomography after human neuronal implantation for stroke. Neurosurgery 2001; 49: 586-591; discussion 591-582.
153. Macas J, Nern C, Plate KH, Momma S. Increased generation of neuronal progenitors after ischemic injury in the aged adult human forebrain. J Neurosci 2006; 26: 13114-13119.
154. Arvidsson A, Collin T, Kirik D, et al. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 2002; 8: 963-970.
155. Nakatomi H, Kuriu T, Okabe S, et al. Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors. Cell 2002; 110: 429-441.
156. Jin K, Wang X, Xie L, et al. Transgenic ablation of doublecortin-expressing cells suppresses adult neurogenesis and worsens stroke outcome in mice. Proc Natl Acad Sci USA 2010; 107: 7993-7998.
157. Chen J, Magavi SS, Macklis JD. Neurogenesis of corticospinal motor neurons extending spinal projections in adult mice. Proc Natl Acad Sci USA 2004; 101: 16357-16362.
158. Park DH, Eve DJ, Sanberg PR, et al. Increased neuronal proliferation in the dentate gyrus of aged rats following neural stem cell implantation. Stem Cells Dev 2010; 19: 175-180.
159. Fricker RA, Carpenter MK, Winkler C, et al. Site-specific migration and neuronal differentiation of human neural progenitor cells after transplantation in the adult rat brain. J Neurosci 1999; 19: 5990-6005.
160. Rossi F, Cattaneo E. Opinion: neural stem cell therapy for neurological diseases: dreams and reality. Nat Rev Neurosci 2002; 3: 401-409.
161. Wictorin K, Brundin P, Gustavii B, et al. Reformation of long axon pathways in adult rat central nervous system by human forebrain neuroblasts. Nature 1990; 347: 556-558.
162. Wictorin K, Brundin P, Sauer H, et al. Long distance directed axonal growth from human dopaminergic mesencephalic neuroblasts implanted along the nigrostriatal pathway in 6-hydroxydopamine lesioned adult rats. J Comp Neurol 1992; 323: 475-494.
163. Isacson O, Deacon TW, Pakzaban P, et al. Transplanted xenogeneic neural cells in neurodegenerative disease models exhibit remarkable axonal target specificity and distinct growth patterns of glial and axonal fibres. Nat Med 1995; 1: 1189-1194.
164. Gaillard A, Decressac M, Frappe I, et al. Anatomical and functional reconstruction of the nigrostriatal pathway by intranigral transplants. Neurobiol Dis 2009; 35: 477-488.
165. Gaillard A, Prestoz L, Dumartin B, et al. Reestablishment of damaged adult motor pathways by grafted embryonic cortical neurons. Nat Neurosci 2007; 10: 1294-1299.
166. Sorensen JC, Grabowski M, Zimmer J, Johansson BB. Fetal neocortical tissue blocks implanted in brain infarcts of adult rats interconnect with the host brain. Exp Neurol 1996; 138: 227-235.
167. Kleppner SR, Robinson KA, Trojanowski JQ, Lee VM. Transplanted human neurons derived from a teratocarcinoma cell line (NTera-2) mature, integrate, and survive for over 1 year in the nude mouse brain. J Comp Neurol 1995; 357: 618-632.
168. McGeer EG, McGeer PL. Substantia nigra cell death from kainic acid or folic acid injections into the pontine tegmentum. Brain Res 1984; 298: 339-342.
169. Daadi MM, Lee SH, Arac A, et al. Functional engraftment of the medial ganglionic eminence cells in experimental stroke model. Cell Transplant 2009; 18: 815-826.
170. Kordower JH, Freeman TB, Snow BJ, et al. Neuropathological evidence of graft survival and striatal reinnervation after the transplantation of fetal mesencephalic tissue in a patient with Parkinson's disease. N Engl J Med 1995; 332: 1118-1124.