The therapeutic potential of neural stem cells

Nature Reviews Neuroscience

Volumn 7, Issue 5, 2006, Pages 395-406

  Martino, Gianvito ^a   Pluchino, Stefano ^a  

^a SAN RAFFAELE HOSPITAL   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

BYSTANDER EFFECT; CELL DIFFERENTIATION; CENTRAL NERVOUS SYSTEM; CENTRAL NERVOUS SYSTEM DISEASE; CYTOARCHITECTURE; HUMAN; INFLAMMATION; INFLAMMATORY CELL; NEURAL STEM CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; STEM CELL; STEM CELL TRANSPLANTATION;

ANIMALS; CELL DIFFERENTIATION; CENTRAL NERVOUS SYSTEM DISEASES; DISEASE MODELS, ANIMAL; HUMANS; MODELS, BIOLOGICAL; NEURONS; STEM CELL TRANSPLANTATION; STEM CELLS;

EID: 33745684551     PISSN: 1471003X     EISSN: 14710048     Source Type: Journal    
DOI: 10.1038/nrn1908     Document Type: Review

References (170)

1. Temple, S. The development of neural stem cells. Nature 414, 112-117 (2001).
2. Gage, F. H. Mammalian neural stem cells. Science 287, 1433-1438 (2000).
3. Ivanova, N. B. et al. A stem cell molecular signature. Science 298, 601-604 (2002).
4. Altman, J. & Das, G. D. Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J. Comp. Neurol. 124, 319-335 (1965).
5. Altman, J. Autoradiographic and histological studies of postnatal neurogenesis. 3. Dating the time of production and onset of differentiation of cerebellar microneurons in rats. J. Comp. Neurol. 136, 269-293 (1969).
6. Doetsch, F. A niche for adult neural stem cells. Curr. Opin. Genet. Dev. 13, 543-550 (2003).
7. Alvarez-Buylla, A. & Lim, D. A. For the long run: maintaining germinal niches in the adult brain. Neuron 41, 683-686 (2004).
8. Garcia, A. D., Doan, N. B., Imura, T., Bush, T. G. & Sofroniew, M. V. GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain. Nature Neurosci. 7, 1233-1241 (2004).
9. Merkle, F. T., Tramontin, A. D., Garcia-Verdugo, J. M. & Alvarez-Buylla, A. Radial glia give rise to adult neural stem cells in the subventricular zone. Proc. Natl Acad. Sci. USA 101, 17528-17532 (2004).
10. Doetsch, F., Caille, I., Lim, D. A., Garcia-Verdugo, J. M. & Alvarez-Buylla, A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97, 703-716 (1999).
11. Gage, F. H., Kempermann, G., Palmer, T. D., Peterson, D. A. & Ray, J. Multipotent progenitor cells in the adult dentate gyrus. J. Neurobiol. 36, 249-266 (1998).
12. Pluchino, S., Zanotti, L., Deleidi, M. & Martino, G. Neural stem cells and their use as therapeutic tool in neurological disorders. Brain Res. Brain Res. Rev. 48, 211-219 (2005).
13. Vescovi, A. L. & Snyder, E. Y. Establishment and properties of neural stem cell clones: plasticity in vitro and in vivo. Brain Pathol. 9, 569-598 (1999).
14. Ming, G. L. & Song, H. Adult neurogenesis in the mammalian central nervous system. Annu. Rev. Neurosci. 28, 223-250 (2005).
15. Zhang, R. L., Zhang, Z. G. & Chopp, M. Neurogenesis in the adult ischemic brain: generation, migration, survival, and restorative therapy. Neuroscientist 11, 408-416 (2005).
16. Brundin, L., Brismar, H., Danilov, A. I., Olsson, T. & Johansson, C. B. Neural stem cells: a potential source for remyelination in neuroinflammatory disease. Brain Pathol. 13, 322-328 (2003).
17. Picard-Riera, N. et al. Experimental autoimmune encephalomyelitis mobilizes neural progenitors from the subventricular zone to undergo oligodendrogenesis in adult mice. Proc. Natl Acad. Sci. USA 99, 13211-13216 (2002).
18. Yagita, Y. et al. Neurogenesis by progenitor cells in the ischemic adult rat hippocampus. Stroke 32, 1890-1896 (2001).
19. Tureyen, K., Vemuganti, R., Sailor, K. A., Bowen, K. K. & Dempsey, R. J. Transient focal cerebral ischemia-induced neurogenesis in the dentate gyrus of the adult mouse. J. Neurosurg. 101, 799-805 (2004).
20. Zhang, R. et al. Stroke transiently increases subventricular zone cell division from asymmetric to symmetric and increases neuronal differentiation in the adult rat. J. Neurosci. 24, 5810-5815 (2004).
21. Carmichael, S. T. Gene expression changes after focal stroke, traumatic brain and spinal cord injuries. Curr. Opin. Neurol. 16, 699-704 (2003).
22. Haas, S., Weidner, N. & Winkler, J. Adult stem cell therapy in stroke. Curr. Opin. Neurol. 18, 59-64 (2005).
23. Lim, D. A. et al. Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 28, 713-726 (2000).
24. Butovsky, O. et al. Microglia activated by IL-4 or IFN-γ differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells. Mol. Cell. Neurosci. 31, 149-160 (2006).
25. Monje, M. L., Toda, H. & Palmer, T. D. Inflammatory blockade restores adult hippocampal neurogenesis. Science 302, 1760-1765 (2003).
26. Vallieres, L., Campbell, I. L., Gage, F. H. & Sawchenko, P. E. Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6. J. Neurosci. 22, 486-492 (2002).
27. Pluchino, S. et al. Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism. Nature 436, 266-271 (2005).
28. Jessell, T. M. & Dodd, J. Floor plate-derived signals and the control of neural cell pattern in vertebrates. Harvey Lect. 86, 87-128 (1990).
29. Seifert, T., Bauer, J., Weissert, R., Fazekas, F. & Storch, M. K. Differential expression of sonic hedgehog immunoreactivity during lesion evolution in autoimmune encephalomyelitis. J. Neuropathol. Exp. Neurol. 64, 404-411 (2005).
30. Irvin, D. K., Nakano, I., Paucar, A. & Kornblum, H. I. Patterns of Jagged1, Jagged2, Delta-like 1 and Delta-like 3 expression during late embryonic and postnatal brain development suggest multiple functional roles in progenitors and differentiated cells. J. Neurosci. Res. 75, 330-343 (2004).
31. John, G. R. et al. Multiple sclerosis: re-expression of a developmental pathway that restricts oligodendrocyte maturation. Nature Med. 8, 1115-1121 (2002).
32. Stidworthy, M. F. et al. Notch1 and Jagged1 are expressed after CNS demyelination, but are not a major rate-determining factor during remyelination. Brain 127, 1928-1941 (2004).
33. Ziv, Y. et al. Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nature Neurosci. 9, 268-275 (2006).
34. Goldman, S. Stem and progenitor cell-based therapy of the human central nervous system. Nature Biotechnol. 23, 862-871 (2005).
35. Goldman, S. A. Directed mobilization of endogenous neural progenitor cells: the intersection of stem cell biology and gene therapy. Curr. Opin. Mol. Ther. 6, 466-472 (2004).
36. Arlotta, P., Magavi, S. S. & Macklis, J. D. Induction of adult neurogenesis: molecular manipulation of neural precursors in situ. Ann. NY Acad. Sci. 991, 229-236 (2003).
37. Emsley, J. G., Mitchell, B. D., Kempermann, G. & Macklis, J. D. Adult neurogenesis and repair of the adult CNS with neural progenitors, precursors, and stem cells. Prog. Neurobiol. 75, 321-341 (2005).
38. Vogel, G. Cell biology. Ready or not? Human ES cells head toward the clinic. Science 308, 1534-1538 (2005).
39. Levenstein, M. E. et al. Basic fibroblast growth factor support of human embryonic stem cell self-renewal. Stem Cells 24, 568-574 (2006).
40. Ludwig, T. E. et al. Derivation of human embryonic stem cells in defined conditions. Nature Biotechnol. 185-187 (2006).
41. Galli, R., Gritti, A., Bonfanti, L. & Vescovi, A. L. Neural stem cells: an overview. Circ. Res. 92, 598-608 (2003).
42. Aboody, K. S. et al. Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc. Natl Acad. Sci. USA 97, 12846-12851 (2000).
43. Müller, F. J., Snyder, E. Y. & Loring, J. F. Gene therapy: can neural stem cells deliver? Nature Rev. Neurosci. 7, 75-84 (2006).
44. Pluchino, S. et al. Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature 422, 688-694 (2003).
45. Einstein, O. et al. Intraventricular transplantation of neural precursor cell spheres attenuates acute experimental allergic encephalomyelitis. Mol. Cell. Neurosci. 24, 1074-1082 (2003).
46. Jeong, S. W. et al. Human neural stem cell transplantation promotes functional recovery in rats with experimental intracerebral hemorrhage. Stroke 34, 2258-2263 (2003).
47. Chu, K., Kim, M., Jeong, S. W., Kim, S. U. & Yoon, B. W. Human neural stem cells can migrate, differentiate, and integrate after intravenous transplantation in adult rats with transient forebrain ischemia. Neurosci. Lett. 343, 129-133 (2003).
48. Fujiwara, Y. et al. Intravenously injected neural progenitor cells of transgenic rats can migrate to the injured spinal cord and differentiate into neurons, astrocytes and oligodendrocytes. Neurosci. Lett. 366, 287-291 (2004).
49. Chu, K. et al. Human neural stem cell transplantation reduces spontaneous recurrent seizures following pilocarpine-induced status epilepticusin adult rats. Brain Res. 1023, 213-221 (2004).
50. Ransohoff, R. M. The chemokine system in neuroinflammation: an update. J. Infect. Dis. 186 (Suppl. 2), S152-S156 (2002).
51. Ben-Hur, T. et al. Transplanted multipotential neural precursor cells migrate into the inflamed white matter in response to experimental autoimmune encephalomyelitis. Glia 41, 73-80 (2003).
52. Campos, L. S., Decker, L., Taylor, V. & Skarnes, W. Notch, epidermal growth factor receptor, and β1-integrin pathways are coordinated in neural stem cells. J. Biol. Chem. 281, 5300-5309 (2006).
53. Campos, L. S. et al. β1 integrins activate a MAPK signalling pathway in neural stem cells that contributes to their maintenance. Development 131, 3433-3444 (2004).
54. Leone, D. P. et al. Regulation of neural progenitor proliferation and survival by β1 integrins. J. Cell Sci. 118, 2589-2599 (2005).
55. Imitola, J. et al. Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1α/CXC chemokine receptor 4 pathway. Proc. Natl Acad. Sci. USA 101, 18117-18122 (2004).
56. Ji, J. F., He, B. P., Dheen, S. T. & Tay, S. S. Expression of chemokine receptors CXCR4, CCR2, CCR5 and CX3CR1 in neural progenitor cells isolated from the subventricular zone of the adult rat brain. Neurosci. Lett. 355, 236-240 (2004).
57. Pluchino, S., Furlan, R. & Martino, G. Cell-based remyelinating therapies in multiple sclerosis: evidence from experimental studies. Curr. Opin. Neurol. 17, 247-255 (2004).
58. Rafuse, V. F., Soundararajan, P., Leopold, C. & Robertson, H. A. Neuroprotective properties of cultured neural progenitor cells are associated with the production of sonic hedgehog. Neuroscience 131, 899-916 (2005).
59. Richardson, R. M., Broaddus, W. C., Holloway, K. L. & Fillmore, H. L. Grafts of adult subependymal zone neuronal progenitor cells rescue hemiparkinsonian behavioral decline. Brain Res. 1032, 11-22 (2005).
60. Ourednik, J., Ourednik, V., Lynch, W. P., Schachner, M. & Snyder, E. Y. Neural stem cells display an inherent mechanism for rescuing dysfunctional neurons. Nature Biotechnol. 20, 1103-1110 (2002).
61. Ryu, J. K. et al. Proactive transplantation of human neural stem cells prevents degeneration of striatal neurons in a rat model of Huntington disease. Neurobiol. Dis. 16, 68-77 (2004).
62. McBride, J. L. et al. Human neural stem cell transplants improve motor function in a rat model of Huntington's disease. J. Comp. Neurol. 475, 211-219 (2004).
63. Tang, Z., Yu, Y., Guo, H. & Zhou, J. Induction of tyrosine hydroxylase expression in rat fetal striatal precursor cells following transplantation. Neurosci. Lett. 324, 13-16 (2002).
64. Hofstetter, C. P. et al. Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome. Nature Neurosci. 8, 346-353 (2005).
65. Chu, K. et al. Human neural stem cells improve sensorimotor deficits in the adult rat brain with experimental focal ischemia. Brain Res. 1016, 145-153 (2004).
66. Cummings, B. J. et al. Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice. Proc. Natl Acad. Sci. USA 102, 14069-14074 (2005).
67. Lu, P., Jones, L. L., Snyder, E. Y. & Tuszynski, M. H. Neural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury. Exp. Neurol. 181, 115-129 (2003).
68. Teng, Y. D. et al. 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).
69. Heine, W., Conant, K., Griffin, J. W. & Hoke, A. Transplanted neural stem cells promote axonal regeneration through chronically denervated peripheral nerves. Exp. Neurol. 189, 231-240 (2004).
70. Kelly, S. et al. Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex. Proc. Natl Acad. Sci. USA 101, 11839-11844 (2004).
71. Park, K. I., Teng, Y. D. & Snyder, E. Y. The injured brain interacts reciprocally with neural stem cells supported by scaffolds to reconstitute lost tissue. Nature Biotechnol. 20, 1111-1117 (2002).
72. Hakuba, N. et al. Neural stem cells suppress the hearing threshold shift caused by cochlear ischemia. Neuroreport 16, 1545-1549 (2005).
73. Mellough, C. B. et al. Fate of multipotent neural precursor cells transplanted into mouse retina selectively depleted of retinal ganglion cells. Exp. Neurol. 186, 6-19 (2004).
74. Micci, M. A. et al. Neural stem cell transplantation in the stomach rescues gastric function in neuronal nitric oxide synthase-deficient mice. Gastroenterology 129, 1817-1824 (2005).
75. Li, L. & Xie, T. Stem cell niche: structure and function. Annu. Rev. Cell Dev. Biol. 21, 605-631 (2005).
76. Zappia, E. et al. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T cell anergy. Blood 106, 1755-1761 (2005).
77. Corcione, A. et al. Human mesenchymal stem cells modulate B-cell functions. Blood 107, 367-372 (2006).
78. Weiss, S. et al. Is there a neural stem cell in the mammalian forebrain? Trends. Neurosci. 19, 387-393 (1996).
79. Laywell, E. D., Rakic, P., Kukekov, V. G., Holland, E. C. & Steindler, D. A. Identification of a multipotent astrocytic stem cell in the immature and adult mouse brain. Proc. Natl Acad. Sci. USA 97, 13883-13888 (2000).
80. Palmer, T. D., Willhoite, A. R. & Gage, F. H. Vascular niche for adult hippocampal neurogenesis. J. Comp. Neurol. 425, 479-494 (2000).
81. Seri, B., Garcia-Verdugo, J. M., McEwen, B. S. & Alvarez-Buylla, A. Astrocytes give rise to new neurons in the adult mammalian hippocampus. J. Neurosci. 21, 7153-7160 (2001).
82. Mercier, F., Kitasako, J. T. & Hatton, G. I. Anatomy of the brain neurogenic zones revisited: fractones and the fibroblast/macrophage network. J. Comp. Neurol. 451, 170-188 (2002).
83. Evans, M. J. & Kaufman, M. H. Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154-156 (1981).
84. Martin, G. R. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc. Natl Acad. Sci. USA 78, 7634-7638 (1981).
85. Thomson, J. A. et al. Isolation of a primate embryonic stem cell line. Proc. Natl Acad. Sci. USA 92, 7844-7848 (1995).
86. Thomson, J. A. et al. Embryonic stem cell lines derived from human blastocysts. Science 282, 1145-1147 (1998).
87. Suda, Y., Suzuki, M., Ikawa, Y. & Aizawa, S. Mouse embryonic stem cells exhibit indefinite proliferative potential. J. Cell Physiol. 133, 197-201 (1987).
88. Conti, L. et al. Niche-independent symmetrical self-renewal of a mammalian tissue stem cell. PLoS Biol. 3, e283 (2005).
89. Zhang, S. C., Wernig, M., Duncan, I. D., Brustle, O. & Thomson, J. A. In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nature Biotechnol. 19, 1129-1133 (2001).
90. Reubinoff, B. E. et al. Neural progenitors from human embryonic stem cells. Nature Biotechnol. 19, 1134-1140 (2001).
91. Hayashi, J. et al. Primate embryonic stem cell-derived neuronal progenitors transplanted into ischemic brain. J. Cereb. Blood Flow Metab. 4 Jan 2006 (doi: 10.1038/sj.jcbfm.9600247).
92. Brustle, O. et al. Embryonic stem cell-derived glial precursors: a source of myelinating transplants. Science 285, 754-756 (1999).
93. Keirstead, H. S. et al. Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J. Neurosci. 25, 4694-4705 (2005).
94. McDonald, J. W. et al. Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nature Med. 5, 1410-1412 (1999).
95. Bjorklund, L. M. et al. Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc. Natl Acad. Sci. USA 99, 2344-2349 (2002).
96. Sanchez-Pernaute, R. et al. Long-term survival of dopamine neurons derived from parthenogenetic primate embryonic stem cells (cyno-1) after transplantation. Stem Cells 23, 914-922 (2005).
97. Ostenfeld, T. et al. Human neural precursor cells express low levels of telomerase in vitro and show diminishing cell proliferation with extensive axonal outgrowth following transplantation. Exp. Neurol. 164, 215-226 (2000).
98. Riess, P. et al. Transplanted neural stem cells survive, differentiate, and improve neurological motor function after experimental traumatic brain injury. Neurosurgery 51, 1043-1052 (2002).
99. Jiang, Y. et al. Neuroectodermal differentiation from mouse multipotent adult progenitor cells. Proc. Natl Acad. Sci. USA 100 (Suppl. 1), 11854-11860 (2003).
100. Suzuki, H. et al. Neurospheres induced from bone marrow stromal cells are multipotent for differentiation into neuron, astrocyte, and oligodendrocyte phenotypes. Biochem. Biophys. Res. Commun. 322, 918-922 (2004).
101. Kogler, G. et al. A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J. Exp. Med. 200, 123-135 (2004).
102. Joannides, A. et al. Efficient generation of neural precursors from adult human skin: astrocytes promote neurogenesis from skin-derived stem cells. Lancet 364, 172-178 (2004).
103. Safford, K. M., Safford, S. D., Gimble, J. M., Shetty, A. K. & Rice, H. E. Characterization of neuronal/glial differentiation of murine adipose-derived adult stromal cells. Exp. Neurol. 187, 319-328 (2004).
104. Safford, K. M. et al. Neurogenic differentiation of murine and human adipose-derived stromal cells. Biochem. Biophys. Res. Commun. 294, 371-379 (2002).
105. Doetsch, F., Garcia-Verdugo, J. M. & Alvarez-Buylla, A. Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J. Neurosci. 17, 5046-5061 (1997).
106. Sanai, N. et al. Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 427, 740-744 (2004).
107. Quinones-Hinojosa, A. et al. Cellular composition and cytoarchitecture of the adult human subventricular zone: a niche of neural stem cells. J. Comp. Neurol. 494, 415-434 (2006).
108. Adams, C. W., Abdulla, Y. H., Torres, E. M. & Poston, R. N. Periventricular lesions in multiple sclerosis: their perivenous origin and relationship to granular ependymitis. Neuropathol. Appl. Neurobiol. 13, 141-152 (1987).
109. Butcher, E. C. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell 67, 1033-1036 (1991).
110. Finley, M. F., Devata, S. & Huettner, J. E. BMP-4 inhibits neural differentiation of murine embryonic stem cells. J. Neurobiol. 40, 271-287 (1999).
111. Tanigaki, K. et al. Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate. Neuron 29, 45-55 (2001).
112. Liem, K. F. Jr, Jessell, T. M. & Briscoe, J. Regulation of the neural patterning activity of sonic hedgehog by secreted BMP inhibitors expressed by notochord and somites. Development 127, 4855-4866 (2000).
113. Rowitch, D. H. et al. Sonic hedgehog regulates proliferation and inhibits differentiation of CNS precursor cells. J. Neurosci. 19, 8954-8965 (1999).
114. Lai, K., Kaspar, B. K., Gage, F. H. & Schaffer, D. V. Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Nature Neurosci. 6, 21-27 (2003).
115. Machold, R. et al. Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches. Neuron 39, 937-950 (2003).
116. Chen, J., Leong, S. Y. & Schachner, M. Differential expression of cell fate determinants in neurons and glial cells of adult mouse spinal cord after compression injury. Eur. J. Neurosci. 22, 1895-1906 (2005).
117. Garcion, E., Halilagic, A., Faissner, A. & ffrench-Constant, C. Generation of an environmental niche for neural stem cell development by the extracellular matrix molecule tenascin C. Development 131, 3423-3432 (2004).
118. Jacques, T. S. et al. Neural precursor cell chain migration and division are regulated through different β1 integrins. Development 125, 3167-3177 (1998).
119. Pesheva, P., Gloor, S., Schachner, M. & Probstmeier, R. Tenascin-R is an intrinsic autocrine factor for oligodendrocyte differentiation and promotes cell adhesion by a sulfatide-mediated mechanism. J. Neurosci. 17, 4642-4651 (1997).
120. Gutowski, N. J., Newcombe, J. & Cuzner, M. L. Tenascin-R and C in multiple sclerosis lesions: relevance to extracellular matrix remodelling. Neuropathol. Appl. Neurobiol. 25, 207-214 (1999).
121. Zhang, Y., Winterbottom, J. K., Schachner, M., Lieberman, A. R. & Anderson, P. N. Tenascin-C expression and axonal sprouting following injury to the spinal dorsal columns in the adult rat. J. Neurosci. Res. 49, 433-450 (1997).
122. 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).
123. Owens, T., Babcock, A. A., Millward, J. M. & Toft-Hansen, H. Cytokine and chemokine interregulation in the inflamed or injured CNS. Brain Res. Brain Res. Rev. 48, 178-184 (2005).
124. Krathwohl, M. D. & Kaiser, J. L. Chemokines promote quiescence and survival of human neural progenitor cells. Stem Cells 22, 109-118 (2004).
125. Reiss, K., Mentlein, R., Sievers, J. & Hartmann, D. Stromal cell-derived factor 1 is secreted by meningeal cells and acts as chemotactic factor on neuronal stem cells of the cerebellar external granular layer. Neuroscience 115, 295-305 (2002).
126. Krumbholz, M. et al. Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain 129, 200-211 (2006).
127. Hill, W. D. 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. 63, 84-96 (2004).
128. Aloisi, F., Ria, F. & Adorini, L. Regulation of T-cell responses by CNS antigen-presenting cells: different roles for microglia and astrocytes. Immunol. Today 21, 141-147 (2000).
129. Storch, A. et al. Long-term proliferation and dopaminergic differentiation of human mesencephalic neural precursor cells. Exp. Neurol. 170, 317-325 (2001).
130. Riaz, S. S., Theofilopoulos, S., Jauniaux, E., Stern, G. M. & Bradford, H. F. The differentiation potential of human foetal neuronal progenitor cells in vitro. Brain Res. Dev. Brain Res. 153, 39-51 (2004).
131. Barnabe-Heider, F. et al. Evidence that embryonic neurons regulate the onset of cortical gliogenesis via cardiotrophin-1. Neuron 48, 253-265 (2005).
132. Ahmed, S., Reynolds, B. A. & Weiss, S. BDNF enhances the differentiation but not the survival of CNS stem cell-derived neuronal precursors. J. Neurosci. 15, 5765-5778 (1995).
133. Kerschensteiner, M. et al. Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J. Exp. Med. 189, 865-870 (1999).
134. Schulte-Herbruggen, O. et al. Tumor necrosis factor-α and interleukin-6 regulate secretion of brain-derived neurotrophic factor in human monocytes. J. Neuroimmunol. 160, 204-209 (2005).
135. Batchelor, P. E. et al. Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. J. Neurosci. 19, 1708-1716 (1999).
136. Stadelmann, C. et al. BDNF and gp145trkB in multiple sclerosis brain lesions: neuroprotective interactions between immune and neuronal cells? Brain 125, 75-85 (2002).
137. Emsley, J. G. & Hagg, T. Endogenous and exogenous ciliary neurotrophic factor enhances forebrain neurogenesis in adult mice. Exp. Neurol. 183, 298-310 (2003).
138. Albrecht, P. J. et al. Astrocytes produce CNTF during the remyelination phase of viral-induced spinal cord demyelination to stimulate FGF-2 production. Neurobiol. Dis. 13, 89-101 (2003).
139. Shingo, T., Sorokan, S. T., Shimazaki, T. & Weiss, S. Erythropoietin regulates the in vitro and in vivo production of neuronal progenitors by mammalian forebrain neural stem cells. J. Neurosci. 21, 9733-9743 (2001).
140. Wang, L. et al. Erythropoietin up-regulates SOCS2 in neuronal progenitor cells derived from SVZ of adult rat. Neuroreport 15, 1225-1229 (2004).
141. Bernaudin, M. et al. A potential role for erythropoietin in focal permanent cerebral ischemia in mice. J. Cereb. Blood Flow Metab. 19, 643-651 (1999).
142. Roussa, E. & Krieglstein, K. GDNF promotes neuronal differentiation and dopaminergic development of mouse mesencephalic neurospheres. Neurosci. Lett. 361, 52-55 (2004).
143. Caggiula, M. et al. Neurotrophic factors in relapsing remitting and secondary progressive multiple sclerosis patients during interferon β therapy. Clin. Immunol. 118, 77-82 (2006).
144. Vargas-Leal, V. et al. Expression and function of glial cell line-derived neurotrophic factor family ligands and their receptors on human immune cells. J. Immunol. 175, 2301-2308 (2005).
145. Forsberg-Nilsson, K., Behar, T. N., Afrakhte, M., Barker, J. L. & McKay, R. D. Platelet-derived growth factor induces chemotaxis of neuroepithelial stem cells. J. Neurosci. Res. 53, 521-530 (1998).
146. Kondo, T. & Raff, M. Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. Science 289, 1754-1757 (2000).
147. Erlandsson, A., Enarsson, M. & Forsberg-Nilsson, K. Immature neurons from CNS stem cells proliferate in response to platelet-derived growth factor. J. Neurosci. 21, 3483-3491 (2001).
148. Hermanson, M., Olsson, T., Westermark, B. & Funa, K. PDGF and its receptors following facial nerve axotomy in rats: expression in neurons and surrounding glia. Exp. Brain Res. 102, 415-422 (1995).
149. Maeda, Y. et al. Platelet-derived growth factor-α receptor-positive oligodendroglia are frequent in multiple sclerosis lesions. Ann. Neurol. 49, 776-785 (2001).
150. Galter, D., Bottner, M. & Unsicker, K. Developmental regulation of the serotonergic transmitter phenotype in rostral and caudal raphe neurons by transforming growth factor-βs. J. Neurosci. Res. 56, 531-538 (1999).
151. Kiefer, R. et al. Transforming growth factor-β1 in experimental autoimmune neuritis. Cellular localization and time course. Am. J. Pathol. 148, 211-223 (1996).
152. Kiefer, R., Schweitzer, T., Jung, S., Toyka, K. V. & Hartung, H. P. Sequential expression of transforming growth factor-β1 by T-cells, macrophages, and microglia in rat spinal cord during autoimmune inflammation. J. Neuropathol. Exp. Neurol. 57, 385-395 (1998).
153. Schanzer, A. et al. Direct stimulation of adult neural stem cells in vitro and neurogenesis in vivo by vascular endothelial growth factor. Brain Pathol. 14, 237-248 (2004).
154. Zhang, H., Vutskits, L., Pepper, M. S. & Kiss, J. Z. VEGF is a chemoattractant for FGF-2-stimulated neural progenitors. J. Cell. Biol. 163, 1375-1384 (2003).
155. Schmidt, N. O. et al. Brain tumor tropism of transplanted human neural stem cells is induced by vascular endothelial growth factor. Neoplasia 7, 623-629 (2005).
156. Proescholdt, M. A., Jacobson, S., Tresser, N., Oldfield, E. H. & Merrill, M. J. Vascular endothelial growth factor is expressed in multiple sclerosis plaques and can induce inflammatory lesions in experimental allergic encephalomyelitis rats. J. Neuropathol. Exp. Neurol. 61, 914-925 (2002).
157. Akiyama, Y. et al. Transplantation of clonal neural precursor cells derived from adult human brain establishes functional peripheral myelin in the rat spinal cord. Exp. Neurol. 167, 27-39 (2001).
158. Shear, D. A. et al. Neural progenitor cell transplants promote long-term functional recovery after traumatic brain injury. Brain Res. 1026, 11-22 (2004).
159. Wong, A. M., Hodges, H. & Horsburgh, K. Neural stem cell grafts reduce the extent of neuronal damage in a mouse model of global ischaemia. Brain Res. 1063, 140-150 (2005).
160. Bjugstad, K. B. et al. Neural stem cells implanted into MPTP-treated monkeys increase the size of endogenous tyrosine hydroxylase-positive cells found in the striatum: a return to control measures. Cell Transplant. 14, 183-192 (2005).
161. Liker, M. A., Petzinger, G. M., Nixon, K., McNeill, T. & Jakowec, M. W. Human neural stem cell transplantation in the MPTP-lesioned mouse. Brain Res. 971, 168-177 (2003).
162. Svendsen, C. N. et al. Long-term survival of human central nervous system progenitor cells transplanted into a rat model of Parkinson's disease. Exp. Neurol. 148, 135-146 (1997).
163. Nishino, H. et al. Mesencephalic neural stem (progenitor) cells develop to dopaminergic neurons more strongly in dopamine-depleted striatum than in intact striatum. Exp. Neurol. 164, 209-214 (2000).
164. 1 integrin during neuronal differentiation of cortical progenitor cells. Exp. Cell Res. 287, 262-271 (2003).
165. Widera, D. et al. MCP-1 induces migration of adult neural stem cells. Eur. J. Cell Biol. 83, 381-387 (2004).
166. Liu, Y. et al. CD44 expression identifies astrocyte-restricted precursor cells. Dev. Biol. 276, 31-46 (2004).
167. Barral-Moran, M. J. et al. Oligodendrocyte progenitor migration in response to injury of glial monolayers requires the polysialic neural cell-adhesion molecule. J. Neurosci. Res. 72, 679-690 (2003).
168. Franceschini, I. et al. Migrating and myelinating potential of neural precursors engineered to overexpress PSA-NCAM. Mol. Cell. Neurosci. 27, 151-162 (2004).
169. Spassky, N. et al. Directional guidance of oligodendroglial migration by class 3 semaphorins and netrin-1. J. Neurosci. 22, 5992-6004 (2002).
170. Sheppard, A. M., McQuillan, J. J., Iademarco, M. F. & Dean, D. C. Control of vascular cell adhesion molecule-1 gene promoter activity during neural differentiation. J. Biol. Chem. 270, 3710-3719 (1995).