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Neural Development and Stem Cells pp 371–419Cite as

Neural Stem Cells and Transplant Therapy

Intrinsic Programs and Clinical Applications

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Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

Approximately two decades ago, it became evident that the developing and adult mammalian central nervous system (CNS) contained a population of neural stem cells (NSCs). These immature, undifferentiated, multipotent cells could be isolated, expanded, and used as cellular vectors for the treatment of neurodegenerative and demyelinating diseases. Their potential as therapeutic agents in a wide range of CNS and peripheral nervous system (PNS) disorders is beginning to be understood. NSCs may give rise to more committed progenitors, such as oligodendrocyte progenitor cells (OPCs), that may also be used as reparative cells. As the “repair” mechanisms by which NSCs act begin to be better elucidated, new therapies may emerge.

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References

  1. Magavi, S. S., Leavitt, B. R., and Macklis, J. D. (2000) Induction of neurogenesis in the neocortex of adult mice [see comments]. Nature 405, 951–955.

    PubMed  CAS  Google Scholar 

  2. Flax, J. D., Aurora, S., Yang, C., et al. (1998) Engraftable human neural stem cells respond to developmental cues, replace neurons, and express foreign genes. Nat. Biotechnol. 16, 1033–1039.

    PubMed  CAS  Google Scholar 

  3. Gokhan, S., Song, Q., and Mehler, M. F. (1998) Generation and regulation of developing immortalized neural cell lines. Methods 16, 345–358.

    PubMed  CAS  Google Scholar 

  4. Johansson, C. B., Momma, S., Clarke, D. L., Risling, M., Lendahl, U., and Frisen, J. (1999) Identification of a neural stem cell in the adult mammalian central nervous system. Cell 96, 25–34.

    PubMed  CAS  Google Scholar 

  5. Mezey, E., Chandross, K. J., Harta, G., Maki, R. A., and McKercher, S. R. (2000) Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow [In Process Citation]. Science 290, 1779–1782.

    PubMed  CAS  Google Scholar 

  6. Roy, N. S., Nakano, T., Keyoung, H. M., et al. (2004) Telomerase immortalization of neuronally restricted progenitor cells derived from the human fetal spinal cord. Nat. Biotechnol. 22, 297–305.

    PubMed  CAS  Google Scholar 

  7. Schuldiner, M., Yanuka, O., Itskovitz-Eldor, J., Melton, D. A., and Benvenisty, N. (2000) From the cover: effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. Proc. Natl. Acad. Sci. USA 97, 11307–11312.

    PubMed  CAS  Google Scholar 

  8. Tamaki, S., Eckert, K., He, D., et al. (2002) Engraftment of sorted/expanded human central nervous system stem cells from fetal brain. J. Neurosci. Res. 69, 976–986.

    PubMed  CAS  Google Scholar 

  9. Gage, F. H. (2000) Mammalian neural stem cells. Science 287, 1433–1438.

    PubMed  CAS  Google Scholar 

  10. Kondo, T. and Raff, M. (2000) Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. Science 289, 1754–1757.

    PubMed  CAS  Google Scholar 

  11. Marmur, R., Mabie, P. C., Gokhan, S., Song, Q., Kessler, J. A., and Mehler, M. F. (1998) Isolation and developmental characterization of cerebral cortical multipotent progenitors. Dev. Biol. 204, 577–591.

    PubMed  CAS  Google Scholar 

  12. Ben-Hur, T., Rogister, B., Murray, K., Rougon, G., and Dubois-Dalcq, M. (1998) Growth and fate of PSA-NCAM+ precursors of the postnatal brain. J. Neurosci. 18, 5777–5788.

    PubMed  CAS  Google Scholar 

  13. Rietze, R. L., Valcanis, H., Brooker, G. F., Thomas, T., Voss, A. K., and Bartlett, P. F. (2001) Purification of a pluripotent neural stem cell from the adult mouse brain. Nature 412, 736–739.

    PubMed  CAS  Google Scholar 

  14. Doetsch, F., Caille, I., Lim, D. A., Garcia-Verdugo, J. M., and Alvarez-Buylla, A. (1999) Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97, 703–716.

    PubMed  CAS  Google Scholar 

  15. Laywell, E. D., Rakic, P., Kukekov, V. G., Holland, E. C., and Steindler, D. A. (2000) Identification of a multipotent astrocytic stem cell in the immature and adult mouse brain. Proc. Natl. Acad. Sci. USA 97, 13883–13888.

    PubMed  CAS  Google Scholar 

  16. Suslov, O. N., Kukekov, V. G., Ignatova, T. N., and Steindler, D. A. (2002) Neural stem cell heterogeneity demonstrated by molecular phenotyping of clonal neurospheres. Proc. Natl. Acad. Sci. USA 99, 14506–14511.

    PubMed  CAS  Google Scholar 

  17. Palmer, T. D., Markakis, E. A., Willhoite, A. R., Safar, F., and Gage, F. H. (1999) Fibro-blast growth factor-2 activates a latent neurogenic program in neural stem cells from diverse regions of the adult CNS. J. Neurosci. 19, 8487–8497.

    PubMed  CAS  Google Scholar 

  18. Lie, D. C., Dziewczapolski, G., Willhoite, A. R., Kaspar, B. K., Shults, C. W., and Gage, F. H. (2002) The adult substantia nigra contains progenitor cells with neurogenic potential. J. Neurosci. 22, 6639–6649.

    PubMed  CAS  Google Scholar 

  19. Alvarez-Buylla, A., and Temple, S. (1998) Stem cells in the developing and adult nervous system. J. Neurobiol. 36, 105–110.

    PubMed  CAS  Google Scholar 

  20. Gage, F. H., Kempermann, G., Palmer, T. D., Peterson, D. A., and Ray, J. (1998) Multipotent progenitor cells in the adult dentate gyrus. J. Neurobiol. 36, 249–266.

    PubMed  CAS  Google Scholar 

  21. Hunter-Schaedle, K. E. (1997) Radial glial cell development and transformation are disturbed in reeler forebrain. J. Neurobiol. 33, 459–472.

    PubMed  CAS  Google Scholar 

  22. Morshead, C. M., Craig, C. G., and van der Kooy, D. (1998) In vivo clonal analyses reveal the properties of endogenous neural stem cell proliferation in the adult mammalian forebrain. Development 125, 2251–2261.

    PubMed  CAS  Google Scholar 

  23. Goldman, J. E., Zerlin, M., Newman, S., Zhang, L., and Gensert, J. (1997) Fate determination and migration of progenitors in the postnatal mammalian CNS. Dev. Neurosci. 19, 42–48.

    PubMed  CAS  Google Scholar 

  24. Levison, S. W. and Goldman, J. E. (1993) Both oligodendrocytes and astrocytes develop from progenitors in the subventricular zone of postnatal rat forebrain. Neuron 10, 201–212.

    PubMed  CAS  Google Scholar 

  25. Ourednik, V., Ourednik, J., Flax, J. D., et al. (2001) Segregation of human neural stem cells in the developing primate forebrain. Science 293, 1820–1824.

    PubMed  CAS  Google Scholar 

  26. Gritti, A., Bonfanti, L., Doetsch, F., et al. (2002) Multipotent neural stem cells reside into the rostral extension and olfactory bulb of adult rodents. J. Neurosci. 22, 437–445.

    PubMed  CAS  Google Scholar 

  27. Nakatomi, H., Kuriu, T., Okabe, S., et al. (2002) Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors. Cell 110, 429–441.

    PubMed  CAS  Google Scholar 

  28. Eriksson, P. S., Perfilieva, E., Bjork-Eriksson, T., et al. (1998) Neurogenesis in the adult human hippocampus [see comments]. Nat. Med. 4, 1313-1317.

    Google Scholar 

  29. van Praag, H., Schinder, A. F., Christie, B. R., Toni, N., Palmer, T. D., and Gage, F. H. (2002) Functional neurogenesis in the adult hippocampus. Nature 415, 1030–1034.

    PubMed  Google Scholar 

  30. Song, H., Stevens, C. F., and Gage, F. H. (2002) Astroglia induce neurogenesis from adult neural stem cells. Nature 417, 39–44.

    PubMed  CAS  Google Scholar 

  31. Song, H. J., Stevens, C. F., and Gage, F. H. (2002) Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons. Nat. Neurosci. 5, 438–445.

    PubMed  CAS  Google Scholar 

  32. Seaberg, R. M. and van der Kooy, D. (2002) Adult rodent neurogenic regions: the ventricular subependyma contains neural stem cells, but the dentate gyrus contains restricted progenitors. J. Neurosci. 22, 1784–1793.

    PubMed  CAS  Google Scholar 

  33. Lois, C. and Alvarez-Buylla, A. (1993) Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. Proc. Natl. Acad. Sci. USA 90, 2074–2077.

    PubMed  CAS  Google Scholar 

  34. Doetsch, F., Petreanu, L., Caille, I., Garcia-Verdugo, J. M., and Alvarez-Buylla, A. (2002) EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells. Neuron 36, 1021–1034.

    PubMed  CAS  Google Scholar 

  35. Doetsch, F., Garcia-Verdugo, J. M., and Alvarez-Buylla, A. (1997) Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J. Neurosci. 17, 5046–5061.

    PubMed  CAS  Google Scholar 

  36. Levison, S. W. and Goldman, J. E. (1997) Multipotential and lineage restricted precursors coexist in the mammalian perinatal subventricular zone. J. Neurosci. Res. 48, 83–94.

    PubMed  CAS  Google Scholar 

  37. Imura, T., Kornblum, H. I., and Sofroniew, M. V. (2003) The predominant neural stem cell isolated from postnatal and adult forebrain but not early embryonic forebrain expresses GFAP. J. Neurosci. 23, 2824–2832.

    PubMed  CAS  Google Scholar 

  38. Morshead, C. M., Reynolds, B. A., Craig, C. G., et al. (1994) Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells. Neuron 13, 1071–1082.

    PubMed  CAS  Google Scholar 

  39. Kirn, J. R., Fishman, Y., Sasportas, K., Alvarez-Buylla, A., and Nottebohm, F. 1999) Fate of new neurons in adult canary high vocal center during the first 30 days after their formation. J. Comp. Neurol. 411, 487–494.

    Google Scholar 

  40. van Praag, H., Christie, B. R., Sejnowski, T. J., and Gage, F. H. (1999) Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc. Natl. Acad. Sci. USA 96, 13427–13431.

    PubMed  Google Scholar 

  41. van Praag, H., Kempermann, G., and Gage, F. H. (1999) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat. Neurosci. 2, 266–270.

    PubMed  Google Scholar 

  42. Shors, T. J., Miesegaes, G., Beylin, A., Zhao, M., Rydel, T., and Gould, E. (2001) Neurogenesis in the adult is involved in the formation of trace memories. Nature 410, 372–376.

    PubMed  CAS  Google Scholar 

  43. Shors, T. J., Townsend, D. A., Zhao, M., Kozorovitskiy, Y., and Gould, E. (2002) Neurogenesis may relate to some but not all types of hippocampal-dependent learning. Hippocampus 12, 578–584.

    PubMed  Google Scholar 

  44. Lendahl, U., Zimmerman, L. B., and McKay, R. D. (1990) CNS stem cells express a new class of intermediate filament protein. Cell 60, 585–595.

    PubMed  CAS  Google Scholar 

  45. Villa, A., Snyder, E. Y., Vescovi, A., and Martinez-Serrano, A. (2000) Establishment and properties of a growth factor-dependent, perpetual neural stem cell line from the human CNS. Exp. Neurol. 161, 67–84.

    PubMed  CAS  Google Scholar 

  46. Lin, R. C. S., Matesic, D. F., Marvin, M., McKay, R. D., and Brustle, O. (1995) Re-expression of the intermediate filament nestin in reactive astrocytes. Neurobiol. Dis. 2, 79–85.

    PubMed  CAS  Google Scholar 

  47. Messam, C. A., Hou, J., and Major, E. O. (2000) Coexpression of nestin in neural and glial cells in the developing human CNS defined by a human-specific anti-nestin antibody. Exp. Neurol. 161, 585–596.

    PubMed  CAS  Google Scholar 

  48. Liu, S., Qu, Y., Stewart, T. J., et al. (2000) Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord transplantation. Proc. Natl. Acad. Sci. USA 97, 6126–6131.

    PubMed  CAS  Google Scholar 

  49. Lumelsky, N., Blondel, O., Laeng, P., Velasco, I., Ravin, R., and McKay, R. (2001) Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 292, 1389–1394.

    PubMed  CAS  Google Scholar 

  50. Zulewski, H., Abraham, E. J., Gerlach, M. J., et al. (2001) Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 50, 521–533.

    PubMed  CAS  Google Scholar 

  51. Shihabuddin, L. S., Ray, J., and Gage, F. H. (1997) FGF-2 is sufficient to isolate progenitors found in the adult mammalian spinal cord. Exp. Neurol. 148, 577–586.

    PubMed  CAS  Google Scholar 

  52. Zerlin, M., Levison, S. W., and Goldman, J. E. (1995) Early patterns of migration, morphogenesis, and intermediate filament expression of subventricular zone cells in the postnatal rat forebrain. J. Neurosci. 15, 7238–7249.

    PubMed  CAS  Google Scholar 

  53. Capela, A. and Temple, S. (2002) LeX/ssea-1 is expressed by adult mouse CNS stem cells, identifying them as nonependymal. Neuron 35, 865–875.

    PubMed  Google Scholar 

  54. Goodell, M. A., Brose, K., Paradis, G., Conner, A. S., and Mulligan, R. C. (1996) Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J. Exp. Med. 183, 1797–1806.

    PubMed  CAS  Google Scholar 

  55. Goodell, M. A., Rosenzweig, M., Kim, H., et al. (1997) Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nat. Med. 3, 1337–1345.

    PubMed  CAS  Google Scholar 

  56. Hulspas, R. and Quesenberry, P. J. (2000) Characterization of neurosphere cell phenotypes by flow cytometry. Cytometry 40, 245–250.

    PubMed  CAS  Google Scholar 

  57. Uchida, N., Buck, D. W., He, D., et al. (2000) Direct isolation of human central nervous system stem cells [In Process Citation]. Proc. Natl. Acad. Sci. USA 97, 14720–14725.

    PubMed  CAS  Google Scholar 

  58. Morrison, S. J., White, P. M., Zock, C., and Anderson, D. J. (1999) Prospective identification, isolation by flow cytometry, and in vivo self-renewal of multipotent mammalian neural crest stem cells. Cell 96, 737–749.

    PubMed  CAS  Google Scholar 

  59. Aboody, K. S., Brown, A., Rainov, N. G., et al. (2000) From the cover: neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas [In Process Citation]. Proc. Natl. Acad. Sci. USA 97, 12846–12851.

    PubMed  CAS  Google Scholar 

  60. Chiasson, B. J., Tropepe, V., Morshead, C. M., and van der Kooy, D. (1999) Adult mammalian forebrain ependymal and subependymal cells demonstrate proliferative potential, but only subependymal cells have neural stem cell characteristics. J. Neurosci. 19, 4462–4471.

    PubMed  CAS  Google Scholar 

  61. Clarke, D. L., Johansson, C. B., Wilbertz, J., et al. (2000) Generalized potential of adult neural stem cells. Science 288, 1660–1663.

    PubMed  CAS  Google Scholar 

  62. McLaren, F. H., Svendsen, C. N., Van der Meide, P., and Joly, E. (2001) Analysis of neural stem cells by flow cytometry: cellular differentiation modifies patterns of MHC expression. J. Neuroimmunol. 112, 35–46.

    PubMed  CAS  Google Scholar 

  63. Hermanson, O., Jepsen, K., and Rosenfeld, M. G. (2002) N-CoR controls differentiation of neural stem cells into astrocytes. Nature 419, 934–939.

    PubMed  CAS  Google Scholar 

  64. Molofsky, A. V., Pardal, R., Iwashita, T., Park, I. K., Clarke, M. F., and Morrison, S. J. (2003) Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 425, 962–967.

    PubMed  CAS  Google Scholar 

  65. Snyder, E. Y. and Vescovi, A. L. (2000) The possibilities/perplexities of stem cells [news]. Nat. Biotechnol. 18, 827–828.

    PubMed  CAS  Google Scholar 

  66. Bjornson, C. R., Rietze, R. L., Reynolds, B. A., Magli, M. C., and Vescovi, A. L. (1999) Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo [see comments]. Science 283, 534–537.

    PubMed  CAS  Google Scholar 

  67. Galli, R., Borello, U., Gritti, A., et al. (2000) Skeletal myogenic potential of human and mouse neural stem cells. Nat. Neurosci. 3, 986–991.

    PubMed  CAS  Google Scholar 

  68. Brazelton, T. R., Rossi, F. M., Keshet, G. I., and Blau, H. M. (2000) From marrow to brain: expression of neuronal phenotypes in adult mice [In Process Citation]. Science 290, 1775–1779.

    PubMed  CAS  Google Scholar 

  69. Morshead, C. M., Benveniste, P., Iscove, N. N., and van der Kooy, D. (2002) Hematopoietic competence is a rare property of neural stem cells that may depend on genetic and epigenetic alterations. Nat. Med. 8, 268–273.

    PubMed  CAS  Google Scholar 

  70. Terada, N., Hamazaki, T., Oka, M., et al. (2002) Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 416, 542–545.

    PubMed  CAS  Google Scholar 

  71. Ying, Q. L., Nichols, J., Evans, E. P., and Smith, A. G. (2002) Changing potency by spontaneous fusion. Nature 416, 545–548.

    PubMed  CAS  Google Scholar 

  72. Weimann, J. M., Charlton, C. A., Brazelton, T. R., Hackman, R. C., and Blau, H. M. (2003) Contribution of transplanted bone marrow cells to Purkinje neurons in human adult brains. Proc. Natl. Acad. Sci. USA 100, 2088–2093.

    PubMed  CAS  Google Scholar 

  73. Niwa, H., Miyazaki, J., and Smith, A. G. (2000) Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet 24, 372–376.

    PubMed  CAS  Google Scholar 

  74. Tsai, R. Y. and McKay, R. D. (2000) Cell contact regulates fate choice by cortical stem cells. J. Neurosci. 20, 3725–3735.

    PubMed  CAS  Google Scholar 

  75. Wagers, A. J., Sherwood, R. I., Christensen, J. L., and Weissman, I. L. (2002) Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 297, 2256–2259.

    PubMed  CAS  Google Scholar 

  76. Alvarez-Dolado, M., Pardal, R., Garcia-Verdugo, J. M., et al. (2003) Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 425, 968–973.

    PubMed  CAS  Google Scholar 

  77. Sanai, N., Tramontin, A. D., Quinones-Hinojosa, A., et al. (2004) Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 427, 740–744.

    PubMed  CAS  Google Scholar 

  78. Palmer, T. D., Schwartz, P. H., Taupin, P., et al. (2001) Cell culture. Progenitor cells from human brain after death. Nature 411, 42–43.

    PubMed  CAS  Google Scholar 

  79. Nunes, M. C., Roy, N. S., Keyoung, H. M., et al. (2003) Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nat. Med. 9, 439–447.

    PubMed  CAS  Google Scholar 

  80. Hardy, R. and Reynolds, R. (1991) Proliferation and differentiation potential of rat fore-brain oligodendroglial progenitors both in vitro and in vivo. Development 111, 1061–1080.

    PubMed  CAS  Google Scholar 

  81. Wu, H. Y., Dawson, M. R., Reynolds, R., and Hardy, R. J. (2001) Expression of QKI proteins and MAP1B identifies actively myelinating oligodendrocytes in adult rat brain. Mol. Cell. Neurosci. 17, 292–302.

    PubMed  CAS  Google Scholar 

  82. Horner, P. J., Power, A. E., Kempermann, G., et al. (2000) Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord. J. Neurosci. 20, 2218–2228.

    PubMed  CAS  Google Scholar 

  83. Yoshimura, K., Sakurai, Y., Nishimura, D., et al. (1998) Monoclonal antibody 14F7, which recognizes a stage-specific immature oligodendrocyte surface molecule, inhibits oligodendrocyte differentiation mediated in co-culture with astrocytes. J. Neurosci. Res. 54, 79–96.

    PubMed  CAS  Google Scholar 

  84. Niehaus, A., Stegmuller, J., Diers-Fenger, M., and Trotter, J. (1999) Cell-surface glycoprotein of oligodendrocyte progenitors involved in migration. J. Neurosci. 19, 4948–4961.

    PubMed  CAS  Google Scholar 

  85. Yu, W. P., Collarini, E. J., Pringle, N. P., and Richardson, W. D. (1994) Embryonic expression of myelin genes: evidence for a focal source of oligodendrocyte precursors in the ventricular zone of the neural tube. Neuron 12, 1353–1362.

    PubMed  CAS  Google Scholar 

  86. Rakic, S. and Zecevic, N. (2003) Early oligodendrocyte progenitor cells in the human fetal telencephalon. Glia 41, 117–127.

    PubMed  Google Scholar 

  87. Lu, Q. R., Yuk, D., Alberta, J. A., et al. (2000) Sonic hedgehog-regulated oligodendrocyte lineage genes encoding bHLH proteins in the mammalian central nervous system. Neuron 25, 317–329.

    PubMed  CAS  Google Scholar 

  88. Nishiyama, A., Chang, A., and Trapp, B. D. (1999) NG2+ glial cells: a novel glial cell population in the adult brain. J. Neuropathol. Exp. Neurol. 58, 1113–1124.

    PubMed  CAS  Google Scholar 

  89. Levine, J. M., Stincone, F., and Lee, Y. S. (1993) Development and differentiation of glial precursor cells in the rat cerebellum. Glia 7, 307–321.

    PubMed  CAS  Google Scholar 

  90. Pouly, S., Prat, A., Blain, M., Olivier, A., and Antel, J. (2001) NG2 immunoreactivity on human brain endothelial cells. Acta Neuropathol. (Berl.) 102, 313–320.

    CAS  Google Scholar 

  91. Jones, L. L., Yamaguchi, Y., Stallcup, W. B., and Tuszynski, M. H. (2002) NG2 is a major chondroitin sulfate proteoglycan produced after spinal cord injury and is expressed by macrophages and oligodendrocyte progenitors. J. Neurosci. 22, 2792–2803.

    PubMed  CAS  Google Scholar 

  92. Reynolds, R. and Hardy, R. (1997) Oligodendroglial progenitors labeled with the O4 antibody persist in the adult rat cerebral cortex in vivo. J. Neurosci. Res. 47, 455–470.

    PubMed  CAS  Google Scholar 

  93. Espinosa de los Monteros, A., Zhang, M., and De Vellis, J. (1993) O2A progenitor cells transplanted into the neonatal rat brain develop into oligodendrocytes but not astrocytes. Proc. Natl. Acad. Sci. USA 90, 50–54.

    PubMed  CAS  Google Scholar 

  94. Gard, A. L. and Pfeiffer, S. E. (1990) Two proliferative stages of the oligodendrocyte lineage (A2B5+O4-and O4+GalC-) under different mitogenic control. Neuron 5, 615–625.

    PubMed  CAS  Google Scholar 

  95. Warrington, A. E., Barbarese, E., and Pfeiffer, S. E. (1993) Differential myelinogenic capacity of specific developmental stages of the oligodendrocyte lineage upon transplantation into hypomyelinating hosts. J. Neurosci. Res. 34, 1–13.

    PubMed  CAS  Google Scholar 

  96. Scolding, N. J., Frith, S., Linington, C., Morgan, B. P., Campbell, A. K., and Compston, D. A. (1989) Myelin-oligodendrocyte glycoprotein (MOG) is a surface marker of oligodendrocyte maturation. J. Neuroimmunol. 22, 169–176.

    PubMed  CAS  Google Scholar 

  97. Shi, J., Marinovich, A., and Barres, B. A. (1998) Purification and characterization of adult oligodendrocyte precursor cells from the rat optic nerve. J. Neurosci. 18, 4627–4636.

    PubMed  CAS  Google Scholar 

  98. Belachew, S., Aguirre, A. A., Wang, H., et al. (2002) Cyclin-dependent kinase-2 controls oligodendrocyte progenitor cell cycle progression and is downregulated in adult oligodendrocyte progenitors. J. Neurosci. 22, 8553–8562.

    PubMed  CAS  Google Scholar 

  99. Wang, S., Sdrulla, A. D., diSibio, G., et al. (1998) Notch receptor activation inhibits oligodendrocyte differentiation. Neuron 21, 63–75.

    PubMed  Google Scholar 

  100. Power, J., Mayer-Proschel, M., Smith, J., and Noble, M. (2002) Oligodendrocyte precursor cells from different brain regions express divergent properties consistent with the differing time courses of myelination in these regions. Dev. Biol. 245, 362–375.

    PubMed  CAS  Google Scholar 

  101. Levison, S. W., Young, G. M., and Goldman, J. E. (1999) Cycling cells in the adult rat neocortex preferentially generate oligodendroglia. J. Neurosci. Res. 57, 435–446.

    PubMed  CAS  Google Scholar 

  102. Ida, J. A., Jr., Dubois-Dalcq, M., and McKinnon, R. D. (1993) Expression of the receptor tyrosine kinase c-kit in oligodendrocyte progenitor cells. J. Neurosci. Res. 36, 596–606.

    PubMed  CAS  Google Scholar 

  103. Patneau, D. K., Wright, P. W., Winters, C., Mayer, M. L., and Gallo, V. (1994) Glial cells of the oligodendrocyte lineage express both kainate-and AMPA-preferring subtypes of glutamate receptor. Neuron 12, 357–371.

    PubMed  CAS  Google Scholar 

  104. Casaccia-Bonnefil, P., Hardy, R. J., Teng, K. K., Levine, J. M., Koff, A., and Chao, M. V. (1999) Loss of p27Kip1 function results in increased proliferative capacity of oligodendrocyte progenitors but unaltered timing of differentiation. Development 126, 4027–4037.

    PubMed  CAS  Google Scholar 

  105. Bergles, D. E., Roberts, J. D., Somogyi, P., and Jahr, C. E. (2000) Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus. Nature 405, 187–191.

    PubMed  CAS  Google Scholar 

  106. Wren, D., Wolswijk, G., and Noble, M. (1992) In vitro analysis of the origin and maintenance of O-2Aadult progenitor cells. J. Cell Biol. 116, 167–176.

    PubMed  CAS  Google Scholar 

  107. Noble, M., Wren, D., and Wolswijk, G. (1992) The O-2A(adult) progenitor cell: a glial stem cell of the adult central nervous system. Semin. Cell Biol. 3, 413–422.

    PubMed  CAS  Google Scholar 

  108. Tang, D. G., Tokumoto, Y. M., Apperly, J. A., Lloyd, A. C., and Raff, M. C. (2001) Lack of replicative senescence in cultured rat oligodendrocyte precursor cells. Science 291, 868–871.

    PubMed  CAS  Google Scholar 

  109. Yoon, S. O., Casaccia-Bonnefil, P., Carter, B., and Chao, M. V. (1998) Competitive signaling between TrkA and p75 nerve growth factor receptors determines cell survival. J. Neurosci. 18, 3273–3281.

    PubMed  CAS  Google Scholar 

  110. Zhang, S. C., Ge, B., and Duncan, I. D. (2000) Tracing human oligodendroglial development in vitro. J. Neurosci. Res. 59, 421–429.

    PubMed  CAS  Google Scholar 

  111. Murray, K. and Dubois-Dalcq, M. (1997) Emergence of oligodendrocytes from human neural spheres. J. Neurosci. Res. 50, 146–156.

    PubMed  CAS  Google Scholar 

  112. Durand, B. and Raff, M. (2000) A cell-intrinsic timer that operates during oligodendrocyte development. Bioessays 22, 64–71.

    PubMed  CAS  Google Scholar 

  113. Windrem, M. S., Nunes, M. C., Rashbaum, W. K., et al. (2004) Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain. Nat. Med. 10, 93–97.

    PubMed  CAS  Google Scholar 

  114. Roy, N. S., Wang, S., Jiang, L., et al. (2000) In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus. Nat. Med. 6, 271–277.

    PubMed  CAS  Google Scholar 

  115. Piper, D. R., Mujtaba, T., Keyoung, H., et al. (2001) Identification and characterization of neuronal precursors and their progeny from human fetal tissue. J. Neurosci. Res. 66, 356–368.

    PubMed  CAS  Google Scholar 

  116. Tourbah, A., Linnington, C., Bachelin, C., Avellana-Adalid, V., Wekerle, H., and Baron-Van Evercooren, A. (1997) Inflammation promotes survival and migration of the CG4 oligodendrocyte progenitors transplanted in the spinal cord of both inflammatory and demyelinated EAE rats. J. Neurosci. Res. 50, 853–861.

    PubMed  CAS  Google Scholar 

  117. Nait-Oumesmar, B., Decker, L., Lachapelle, F., Avellana-Adalid, V., Bachelin, C., and Van Evercooren, A. B. (1999) Progenitor cells of the adult mouse subventricular zone proliferate, migrate and differentiate into oligodendrocytes after demyelination. Eur. J. Neurosci. 11, 4357–4366.

    PubMed  CAS  Google Scholar 

  118. Conover, J. C., Doetsch, F., Garcia-Verdugo, J. M., Gale, N. W., Yancopoulos, G. D., and Alvarez-Buylla, A. (2000) Disruption of Eph/ephrin signaling affects migration and proliferation in the adult subventricular zone. Nat. Neurosci. 3, 1091–1097.

    PubMed  CAS  Google Scholar 

  119. Forsberg-Nilsson, K., Behar, T. N., Afrakhte, M., Barker, J. L., and McKay, R. D. (1998) Platelet-derived growth factor induces chemotaxis of neuroepithelial stem cells. J. Neurosci. Res. 53, 521–530.

    PubMed  CAS  Google Scholar 

  120. Pluchino, S., Quattrini, A., Brambilla, E., et al. (2003) Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature 422, 688–694.

    PubMed  CAS  Google Scholar 

  121. Liu, Y., Himes, B. T., Solowska, J., et al. (1999) Intraspinal delivery of neurotrophin-3 using neural stem cells genetically modified by recombinant retrovirus. Exp. Neurol. 158, 9–26.

    PubMed  CAS  Google Scholar 

  122. Snyder, E. Y., Yoon, C., Flax, J. D., and Macklis, J. D. (1997) Multipotent neural precursors can differentiate toward replacement of neurons undergoing targeted apoptotic degeneration in adult mouse neocortex. Proc. Natl. Acad. Sci. USA 94, 11663–11668.

    PubMed  CAS  Google Scholar 

  123. Park, K. I., Liu, S., Flax, J. D., Nissim, S., Stieg, P. E., and Snyder, E. Y. (1999) Transplantation of neural progenitor and stem cells: developmental insights may suggest new therapies for spinal cord and other CNS dysfunction. J. Neurotrauma 16, 675–687.

    PubMed  CAS  Google Scholar 

  124. Park, K. I., Teng, Y. D., and Snyder, E. Y. (2002) The injured brain interacts reciprocally with neural stem cells supported by scaffolds to reconstitute lost tissue. Nat. Biotechnol. 20, 1111–1117.

    PubMed  CAS  Google Scholar 

  125. Fukunaga, A., Uchida, K., Hara, K., Kuroshima, Y., and Kawase, T. (1999) Differentiation and angiogenesis of central nervous system stem cells implanted with mesenchyme into ischemic rat brain. Cell Transplant. 8, 435–441.

    PubMed  CAS  Google Scholar 

  126. Andsberg, G., Kokaia, Z., Bjorklund, A., Lindvall, O., and Martinez-Serrano, A. (1998) Amelioration of ischaemia-induced neuronal death in the rat striatum by NGF-secreting neural stem cells. Eur. J. Neurosci. 10, 2026–2036.

    PubMed  CAS  Google Scholar 

  127. Toda, H., Takahashi, J., Iwakami, N., et al. (2001) Grafting neural stem cells improved the impaired spatial recognition in ischemic rats. Neurosci. Lett. 316, 9–12.

    PubMed  CAS  Google Scholar 

  128. Riess, P., Zhang, C., Saatman, K. E., et al. (2002) Transplanted neural stem cells survive, differentiate, and improve neurological motor function after experimental traumatic brain injury. Neurosurgery 51, 1043–1052; discussion 1052–1044.

    PubMed  Google Scholar 

  129. Auerbach, J. M., Eiden, M. V., and McKay, R. D. (2000) Transplanted CNS stem cells form functional synapses in vivo. Eur. J. Neurosci. 12, 1696–1704.

    PubMed  CAS  Google Scholar 

  130. Song, H. J., Stevens, C. F., and Gage, F. H. (2002) Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons. Nat. Neurosci. 5, 438–445.

    PubMed  CAS  Google Scholar 

  131. Lundberg, C., Englund, U., Trono, D., Bjorklund, A., and Wictorin, K. (2002) Differentiation of the RN33B cell line into forebrain projection neurons after transplantation into the neonatal rat brain. Exp. Neurol. 175, 370–387.

    PubMed  CAS  Google Scholar 

  132. Yamamoto, S., Nagao, M., Sugimori, M., et al. (2001) Transcription factor expression and Notch-dependent regulation of neural progenitors in the adult rat spinal cord. J. Neuro-sci. 21, 9814–9823.

    CAS  Google Scholar 

  133. Vroemen, M., Aigner, L., Winkler, J., and Weidner, N. (2003) Adult neural progenitor cell grafts survive after acute spinal cord injury and integrate along axonal pathways. Eur. J. Neurosci. 18, 743–751.

    PubMed  Google Scholar 

  134. Bambakidis, N. C. and Miller, R. H. (2004) Transplantation of oligodendrocyte precursors and sonic hedgehog results in improved function and white matter sparing in the spinal cords of adult rats after contusion. Spine J. 4, 16–26.

    PubMed  Google Scholar 

  135. Schumm, M. A., Castellanos, D. A., Frydel, B. R., and Sagen, J. (2004) Improved neural progenitor cell survival when cografted with chromaffin cells in the rat striatum. Exp. Neurol. 185, 133–142.

    PubMed  CAS  Google Scholar 

  136. Schumm, M. A., Castellanos, D. A., Frydel, B. R., and Sagen, J. (2003) Direct cell-cell contact required for neurotrophic effect of chromaffin cells on neural progenitor cells. Brain Res. Dev. Brain Res. 146, 1–13.

    PubMed  CAS  Google Scholar 

  137. Ourednik, J., Ourednik, V., Lynch, W. P., Schachner, M., and Snyder, E. Y. (2002) Neural stem cells display an inherent mechanism for rescuing dysfunctional neurons. Nat. Biotechnol. 20, 1103–1110.

    PubMed  CAS  Google Scholar 

  138. Hagan, M., Wennersten, A., Meijer, X., Holmin, S., Wahlberg, L., and Mathiesen, T. (2003) Neuroprotection by human neural progenitor cells after experimental contusion in rats. Neurosci. Lett. 351, 149–152.

    PubMed  CAS  Google Scholar 

  139. Lu, P., Jones, L. L., Snyder, E. Y., and Tuszynski, M. H. (2003) Neural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury. Exp. Neurol. 181, 115–129.

    PubMed  CAS  Google Scholar 

  140. Hains, B. C., Johnson, K. M., Eaton, M. J., Willis, W. D., and Hulsebosch, C. E. (2003) Serotonergic neural precursor cell grafts attenuate bilateral hyperexcitability of dorsal horn neurons after spinal hemisection in rat. Neuroscience 116, 1097–1110.

    PubMed  CAS  Google Scholar 

  141. Teng, Y. D., Lavik, E. B., Qu, X., et al. (2002) 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.

    PubMed  CAS  Google Scholar 

  142. Haughey, N. J., Nath, A., Chan, S. L., Borchard, A. C., Rao, M. S., and Mattson, M. P. (2002) Disruption of neurogenesis by amyloid beta-peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer’s disease. J. Neurochem. 83, 1509–1524.

    PubMed  CAS  Google Scholar 

  143. Mehta, V., Hong, M., Spears, J., and Mendez, I. (1998) Enhancement of graft survival and sensorimotor behavioral recovery in rats undergoing transplantation with dopaminergic cells exposed to glial cell line-derived neurotrophic factor. J. Neurosurg. 88, 1088–1095.

    PubMed  CAS  Google Scholar 

  144. Lindvall, O. (2000) Neural transplantation in Parkinson’s disease. Novartis Found. Symp. 231, 110–123; discussion 123–118, 145–117.

    PubMed  CAS  Google Scholar 

  145. Piccini, P., Lindvall, O., Bjorklund, A., et al. (2000) Delayed recovery of movement-related cortical function in Parkinson’s disease after striatal dopaminergic grafts. Ann. Neurol. 48, 689–695.

    PubMed  CAS  Google Scholar 

  146. Anton, R., Kordower, J. H., Maidment, N. T., et al. (1994) Neural-targeted gene therapy for rodent and primate hemiparkinsonism. Exp. Neurol. 127, 207–218.

    PubMed  CAS  Google Scholar 

  147. Lundberg, C., Field, P. M., Ajayi, Y. O., Raisman, G., and Bjorklund, A. (1996) Conditionally immortalized neural progenitor cell lines integrate and differentiate after grafting to the adult rat striatum. A combined autoradiographic and electron microscopic study. Brain Res. 737, 295–300.

    PubMed  CAS  Google Scholar 

  148. Zigova, T., Pencea, V., Betarbet, R., et al. (1998) Neuronal progenitor cells of the neonatal subventricular zone differentiate and disperse following transplantation into the adult rat striatum. Cell Transplant. 7, 137–156.

    PubMed  CAS  Google Scholar 

  149. Sun, Z. H., Lai, Y. L., Zeng, W. W., et al. (2003) Mesencephalic progenitors can improve rotational behavior and reconstruct nigrostriatal pathway in PD rats. Acta Neurochir. Suppl. 87, 175–180.

    PubMed  CAS  Google Scholar 

  150. Yang, M., Stull, N. D., Berk, M. A., Snyder, E. Y., and Iacovitti, L. (2002) Neural stem cells spontaneously express dopaminergic traits after transplantation into the intact or 6-hydroxydopamine-lesioned rat. Exp. Neurol. 177, 50–60.

    PubMed  CAS  Google Scholar 

  151. Studer, L., Tabar, V., and McKay, R. D. (1998) Transplantation of expanded mesencephalic precursors leads to recovery in parkinsonian rats. Nat. Neurosci. 1, 290–295.

    PubMed  CAS  Google Scholar 

  152. Matsuura, N., Lie, D. C., Hoshimaru, M., et al. (2001) Sonic hedgehog facilitates dopamine differentiation in the presence of a mesencephalic glial cell line. J. Neurosci. 21, 4326–4335.

    PubMed  CAS  Google Scholar 

  153. Bjugstad, K. B., Redmond, D. E., Teng, Y. D., Elsworth, J. D., Roth, R. H., Blanchard, B. C., Snyder, E. Y., Sledek, J. R. Neural stem cells implanted into MPTP-treated monkeys increases the size of endogenous tyrosine-hydroxylase-positive cells found in the caudate. Cell Transplantation (in press).

    Google Scholar 

  154. Dziewczapolski, G., Lie, D. C., Ray, J., Gage, F. H., and Shults, C. W. (2003) Survival and differentiation of adult rat-derived neural progenitor cells transplanted to the striatum of hemiparkinsonian rats. Exp. Neurol. 183, 653–664.

    PubMed  CAS  Google Scholar 

  155. Kim, J. H., Auerbach, J. M., Rodriguez-Gomez, J. A., et al. (2002) Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature 418, 50–56.

    PubMed  CAS  Google Scholar 

  156. Kawasaki, H., Suemori, H., Mizuseki, K., et al. (2002) Generation of dopaminergic neurons and pigmented epithelia from primate ES cells by stromal cell-derived inducing activity. Proc. Natl. Acad. Sci. USA 99, 1580–1585.

    PubMed  CAS  Google Scholar 

  157. Kawasaki, H., Mizuseki, K., Nishikawa, S., et al. (2000) Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron 28, 31–40.

    PubMed  CAS  Google Scholar 

  158. Svendsen, C. N., Caldwell, M. A., Shen, J., et al. (1997) Long-term survival of human central nervous system progenitor cells transplanted into a rat model of Parkinson’s disease. Exp. Neurol. 148, 135–146.

    PubMed  CAS  Google Scholar 

  159. Kordower, J. H., Chen, E. Y., Winkler, C., et al. (1997) Grafts of EGF-responsive neural stem cells derived from GFAP-hNGF transgenic mice: trophic and tropic effects in a rodent model of Huntington’s disease. J. Comp. Neurol. 387, 96–113.

    PubMed  CAS  Google Scholar 

  160. Martinez-Serrano, A., Fischer, W., and Bjorklund, A. (1995) Reversal of age-dependent cognitive impairments and cholinergic neuron atrophy by NGF-secreting neural progenitors grafted to the basal forebrain. Neuron 15, 473–484.

    PubMed  CAS  Google Scholar 

  161. Noseworthy, J. H., Lucchinetti, C., Rodriguez, M., and Weinshenker, B. G. (2000) Multiple sclerosis. N. Engl. J. Med. 343, 938–952.

    PubMed  CAS  Google Scholar 

  162. De Stefano, N., Narayanan, S., Francis, G. S., et al. (2001) Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability. Arch. Neurol. 58, 65–70.

    PubMed  Google Scholar 

  163. Lucchinetti, C., Bruck, W., Parisi, J., Scheithauer, B., Rodriguez, M., and Lassmann, H. (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann. Neurol. 47, 707–717.

    PubMed  CAS  Google Scholar 

  164. Scolding, N. J., Rayner, P. J., and Compston, D. A. (1999) Identification of A2B5-posi-tive putative oligodendrocyte progenitor cells and A2B5-positive astrocytes in adult human white matter. Neuroscience 89, 1–4.

    PubMed  CAS  Google Scholar 

  165. Scolding, N., Franklin, R., Stevens, S., Heldin, C. H., Compston, A., and Newcombe, J. (1998) Oligodendrocyte progenitors are present in the normal adult human CNS and in the lesions of multiple sclerosis. Brain 121, 2221–2228.

    PubMed  Google Scholar 

  166. Catanzaro, M. and Weinert, C. (1992) Economic status of families living with multiple sclerosis. Int. J. Rehabil. Res. 15, 209–218.

    PubMed  CAS  Google Scholar 

  167. Yandava, B. D., Billinghurst, L. L., and Snyder, E. Y. (1999) “Global” cell replacement is feasible via neural stem cell transplantation: evidence from the dysmyelinated shiverer mouse brain. Proc. Natl. Acad. Sci. USA 96, 7029–7034.

    PubMed  CAS  Google Scholar 

  168. Hammang, J. P., Archer, D. R., and Duncan, I. D. (1997) Myelination following transplantation of EGF-responsive neural stem cells into a myelin-deficient environment. Exp. Neurol. 147, 84–95.

    PubMed  CAS  Google Scholar 

  169. Milward, E. A., Lundberg, C. G., Ge, B., Lipsitz, D., Zhao, M., and Duncan, I. D. (1997) Isolation and transplantation of multipotential populations of epidermal growth factor-responsive, neural progenitor cells from the canine brain. J. Neurosci. Res. 50, 862–871.

    PubMed  CAS  Google Scholar 

  170. Akiyama, Y., Honmou, O., Kato, T., Uede, T., Hashi, K., and Kocsis, J. D. (2001) 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.

    PubMed  CAS  Google Scholar 

  171. Brustle, O., Jones, K. N., Learish, R. D., et al. (1999) Embryonic stem cell-derived glial precursors: a source of myelinating transplants. Science 285, 754–756.

    PubMed  CAS  Google Scholar 

  172. Archer, D. R., Cuddon, P. A., Lipsitz, D., and Duncan, L. D. (1997) Myelination of the canine central nervous system by glial cell transplantation: a model for repair of human myelin disease. Nat. Med. 3, 54–59.

    PubMed  CAS  Google Scholar 

  173. Espinosa de los Monteros, A., Zhao, P., Huang, C., et al. (1997) Transplantation of CG4 oligodendrocyte progenitor cells in the myelin-deficient rat brain results in myelination of axons and enhanced oligodendroglial markers. J. Neurosci. Res. 50, 872–887.

    PubMed  CAS  Google Scholar 

  174. Zhang, S. C., Ge, B., and Duncan, I. D. (1999) Adult brain retains the potential to generate oligodendroglial progenitors with extensive myelination capacity. Proc. Natl. Acad. Sci. USA 96, 4089–4094.

    PubMed  CAS  Google Scholar 

  175. Smith, P. M. and Blakemore, W. F. (2000) Porcine neural progenitors require commitment to the oligodendrocyte lineage prior to transplantation in order to achieve significant remyelination of demyelinated lesions in the adult CNS. Eur. J. Neurosci. 12, 2414–2424.

    PubMed  CAS  Google Scholar 

  176. Imaizumi, T., Lankford, K. L., Burton, W. V., Fodor, W. L., and Kocsis, J. D. (2000) Xenotransplantation of transgenic pig olfactory ensheathing cells promotes axonal regeneration in rat spinal cord. Nat. Biotechnol. 18, 949–953.

    PubMed  CAS  Google Scholar 

  177. Kato, T., Honmou, O., Uede, T., Hashi, K., and Kocsis, J. D. (2000) Transplantation of human olfactory ensheathing cells elicits remyelination of demyelinated rat spinal cord. Glia 30, 209–218.

    PubMed  CAS  Google Scholar 

  178. Barnett, S. C., Alexander, C. L., Iwashita, Y., et al. (2000) Identification of a human olfactory ensheathing cell that can effect transplant-mediated remyelination of demyelinated CNS axons. Brain 123(Pt 8), 1581–1588.

    PubMed  Google Scholar 

  179. Kohama, I., Lankford, K. L., Preiningerova, J., White, F. A., Vollmer, T. L., and Kocsis, J. D. (2001) Transplantation of cryopreserved adult human Schwann cells enhances axonal conduction in demyelinated spinal cord. J. Neurosci. 21, 944–950.

    PubMed  CAS  Google Scholar 

  180. Franklin, R. J. and Blakemore, W. F. 1997) Transplanting oligodendrocyte progenitors into the adult CNS. J. Anat. 190, 23–33.

    Google Scholar 

  181. Rosario, C. M., Yandava, B. D., Kosaras, B., Zurakowski, D., Sidman, R. L., and Snyder, E. Y. (1997) Differentiation of engrafted multipotent neural progenitors towards replacement of missing granule neurons in meander tail cerebellum may help determine the locus of mutant gene action. Development 124, 4213–4224.

    PubMed  CAS  Google Scholar 

  182. Snyder, E. Y., Taylor, R. M., and Wolfe, J. H. (1995) Neural progenitor cell engraftment corrects lysosomal storage throughout the MPS VII mouse brain. Nature 374, 367–370.

    PubMed  CAS  Google Scholar 

  183. Lacorazza, H. D., Flax, J. D., Snyder, E. Y., and Jendoubi, M. (1996) Expression of human beta-hexosaminidase alpha-subunit gene (the gene defect of Tay-Sachs disease) in mouse brains upon engraftment of transduced progenitor cells. Nat. Med. 2, 424–429.

    PubMed  CAS  Google Scholar 

  184. Torchiana, E., Lulli, L., Cattaneo, E., et al. (1998) Retroviral-mediated transfer of the galactocerebrosidase gene in neural progenitor cells. NeuroReport 9, 3823–3827.

    PubMed  CAS  Google Scholar 

  185. Meng, X. L., Shen, J. S., Ohashi, T., Maeda, H., Kim, S. U., and Eto, Y. (2003) Brain transplantation of genetically engineered human neural stem cells globally corrects brain lesions in the mucopolysaccharidosis type VII mouse. J. Neurosci. Res. 74, 266–277.

    PubMed  CAS  Google Scholar 

  186. Tamura, T., Nakagawa, T., Iguchi, F., et al. (2004) Transplantation of neural stem cells into the modiolus of mouse cochleae injured by cisplatin. Acta Otolaryngol. Suppl. 65–68.

    Google Scholar 

  187. Mellough, C. B., Cui, Q., Spalding, K. L., et al. (2004) Fate of multipotent neural precursor cells transplanted into mouse retina selectively depleted of retinal ganglion cells. Exp. Neurol. 186, 6–19.

    PubMed  Google Scholar 

  188. Ehtesham, M., Kabos, P., Gutierrez, M. A., et al. (2002) Induction of glioblastoma apoptosis using neural stem cell-mediated delivery of tumor necrosis factor-related apoptosis-inducing ligand. Cancer Res. 62, 7170–7174.

    PubMed  CAS  Google Scholar 

  189. Ehtesham, M., Kabos, P., Kabosova, A., Neuman, T., Black, K. L., and Yu, J. S. (2002) The use of interleukin 12-secreting neural stem cells for the treatment of intracranial glioma. Cancer Res. 62, 5657–5663.

    Google Scholar 

  190. Benedetti, S., Pirola, B., Pollo, B., et al. (2000) Gene therapy of experimental brain tumors using neural progenitor cells. Nat. Med. 6, 447–450.

    PubMed  CAS  Google Scholar 

  191. Nakafuku, M. and Nakamura, S. (1995) Establishment and characterization of a multipotential neural cell line that can conditionally generate neurons, astrocytes, and oligodendrocytes in vitro. J. Neurosci. Res. 41, 153–168.

    PubMed  CAS  Google Scholar 

  192. Hulspas, R., Tiarks, C., Reilly, J., Hsieh, C. C., Recht, L., and Quesenberry, P. J. (1997) In vitro cell density-dependent clonal growth of EGF-responsive murine neural progenitor cells under serum-free conditions. Exp. Neurol. 148, 147–156.

    PubMed  CAS  Google Scholar 

  193. Ryder, E. F., Snyder, E. Y., and Cepko, C. L. (1990) Establishment and characterization of multipotent neural cell lines using retro virus vector-mediated oncogene transfer. J. Neuro-biol. 21, 356–375.

    CAS  Google Scholar 

  194. Bjorklund, A. and Lindvall, O. (2000) Cell replacement therapies for central nervous system disorders. Nat. Neurosci. 3, 537–544.

    PubMed  CAS  Google Scholar 

  195. Monje, M. L., Mizumatsu, S., Fike, J. R., and Palmer, T. D. (2002) Irradiation induces neural precursor-cell dysfunction. Nat. Med. 8, 955–962.

    PubMed  CAS  Google Scholar 

  196. Monje, M. L., Toda, H., and Palmer, T. D. (2003) Inflammatory blockade restores adult hippocampal neurogenesis. Science 302, 1760–1765.

    PubMed  CAS  Google Scholar 

  197. Imitola, J., Comabella, M., Chandraker, A. K., et al. (2004) Neural stem/progenitor cells express costimulatory molecules that are differentially regulated by inflammatory and apoptotic stimuli. Am. J. Pathol. 164, 1615–1625.

    PubMed  CAS  Google Scholar 

  198. Imitola, J., Snyder, E. Y., and Khoury, S. J. (2003) Genetic programs and responses of neural stem/progenitor cells during demyelination: potential insights into repair mechanisms in multiple sclerosis. Physiol. Genom. 14, 171–197.

    CAS  Google Scholar 

  199. Gensert, J. M. and Goldman, J. E. (1997) Endogenous progenitors remyelinate demyelinated axons in the adult CNS. Neuron 19, 197–203.

    PubMed  CAS  Google Scholar 

  200. Wolswijk, G. (1998) Chronic stage multiple sclerosis lesions contain a relatively quiescent population of oligodendrocyte precursor cells. J. Neurosci. 18, 601–609.

    PubMed  CAS  Google Scholar 

  201. Rogister, B., Ben-Hur, T., and Dubois-Dalcq, M. (1999) From neural stem cells to myelinating oligodendrocytes. Mol. Cell. Neurosci. 14, 287–300.

    PubMed  CAS  Google Scholar 

  202. Fallon, J., Reid, S., Kinyamu, R., et al. (2000) In vivo induction of massive proliferation, directed migration, and differentiation of neural cells in the adult mammalian brain [In Process Citation]. Proc. Natl. Acad. Sci. USA 97, 14686–14691.

    PubMed  CAS  Google Scholar 

  203. Cannella, B., Hoban, C. J., Gao, Y. L., et al. (1998) The neuregulin, glial growth factor 2, diminishes autoimmune demyelination and enhances remyelination in a chronic relapsing model for multiple sclerosis. Proc. Natl. Acad. Sci. USA 95, 10100–10105.

    PubMed  CAS  Google Scholar 

  204. Cannella, B., Pitt, D., Marchionni, M., and Raine, C. S. (1999) Neuregulin and erbB receptor expression in normal and diseased human white matter. J. Neuroimmunol. 100, 233–242.

    PubMed  CAS  Google Scholar 

  205. Martens, D. J., Seaberg, R. M., and van der Kooy, D. (2002) 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. 16, 1045–1057.

    PubMed  Google Scholar 

  206. Kuhn, H. G., Winkler, J., Kempermann, G., Thal, L. J., and Gage, F. H. (1997) Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain. J. Neurosci. 17, 5820–5829.

    PubMed  CAS  Google Scholar 

  207. Snyder, E. Y., Deitcher, D. L., Walsh, C., Arnold-Aldea, S., Hartwieg, E. A., and Cepko, C. L. (1992) Multipotent neural cell lines can engraft and participate in development of mouse cerebellum. Cell 68, 33–51.

    PubMed  CAS  Google Scholar 

  208. Tang, Y., Shah, K., Messerli, S. M., Snyder, E., Breakefield, X., and Weissleder, R. (2003) In vivo tracking of neural progenitor cell migration to glioblastomas. Hum. Gene Ther. 14, 1247–1254.

    PubMed  CAS  Google Scholar 

  209. Rothstein, J. D. and Snyder, E. Y. (2004) Reality and immortality-neural stem cells for therapies. Nat. Biotechnol. 22, 283–285.

    PubMed  CAS  Google Scholar 

  210. Wu, P., Tarasenko, Y. I., Gu, Y., Huang, L. Y., Coggeshall, R. E., and Yu, Y. (2002) Region-specific generation of cholinergic neurons from fetal human neural stem cells grafted in adult rat. Nat. Neurosci. 5, 1271–1278.

    PubMed  CAS  Google Scholar 

  211. Fricker, R. A., Carpenter, M. K., Winkler, C., Greco, C., Gates, M. A., and Bjorklund, A. (1999) Site-specific migration and neuronal differentiation of human neural progenitor cells after transplantation in the adult rat brain. J. Neurosci. 19, 5990–6005.

    PubMed  CAS  Google Scholar 

  212. Brustle, O., Choudhary, K., Karram, K., et al. (1998) Chimeric brains generated by intra-ventricular transplantation of fetal human brain cells into embryonic rats. Nat. Biotechnol. 16, 1040–1044.

    PubMed  CAS  Google Scholar 

  213. Bulte, J. W., Douglas, T., Witwer, B., et al. (2001) Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nat. Biotechnol. 19, 1141–1147.

    PubMed  CAS  Google Scholar 

  214. Bulte, J. W., Zhang, S., van Gelderen, P., et al. (1999) Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination. Proc. Natl. Acad. Sci. USA 96, 15256–15261.

    PubMed  CAS  Google Scholar 

  215. Bulte, J. W., Ben-Hur, T., Miller, B. R., et al. (2003) MR microscopy of magnetically labeled neurospheres transplanted into the Lewis EAE rat brain. Magn. Reson. Med. 50, 201–205.

    PubMed  Google Scholar 

  216. Modo, M., Mellodew, K., Cash, D., et al. (2004) Mapping transplanted stem cell migration after a stroke: a serial, in vivo magnetic resonance imaging study. Neuroimage 21, 311–317.

    PubMed  Google Scholar 

  217. Kim, D. E., Schellingerhout, D., Ishii, K., Shah, K., and Weissleder, R. (2004) Imaging of stem cell recruitment to ischemic infarcts in a murine model. Stroke 35, 952–957.

    PubMed  Google Scholar 

  218. Ben-Hur, T., Einstein, O., Mizrachi-Kol, R., et al. (2003) Transplanted multipotential neural precursor cells migrate into the inflamed white matter in response to experimental autoimmune encephalomyelitis. Glia 41, 73–80.

    PubMed  Google Scholar 

  219. Zhang, S. C., Goetz, B. D., and Duncan, I. D. (2003) Suppression of activated microglia promotes survival and function of transplanted oligodendroglial progenitors. Glia 41, 191–198.

    PubMed  Google Scholar 

  220. Isenmann, S., Brandner, S., Kuhne, G., Boner, J., and Aguzzi, A. (1996) Comparative in vivo and pathological analysis of the blood-brain barrier in mouse telencephalic transplants. Neuropathol. Appl. Neurobiol. 22, 118–128.

    PubMed  CAS  Google Scholar 

  221. Kinouchi, R., Takeda, M., Yang, L., et al. (2003) Robust neural integration from retinal transplants in mice deficient in GFAP and vimentin. Nat. Neurosci. 6, 863–868.

    PubMed  CAS  Google Scholar 

  222. Akerud, P., Canals, J. M., Snyder, E. Y., and Arenas, E. (2001) Neuroprotection through delivery of glial cell line-derived neurotrophic factor by neural stem cells in a mouse model of Parkinson’s disease. J. Neurosci. 21, 8108–8118.

    PubMed  CAS  Google Scholar 

  223. Calza, L., Giardino, L., Pozza, M., Bettelli, C., Micera, A., and Aloe, L. (1998) Proliferation and phenotype regulation in the subventricular zone during experimental allergic encephalomyelitis: in vivo evidence of a role for nerve growth factor. Proc. Natl. Acad. Sci. USA 95, 3209–3214.

    PubMed  CAS  Google Scholar 

  224. Himes, B. T., Liu, Y., Solowska, J. M., Snyder, E. Y., Fischer, I., and Tessler, A. (2001) Transplants of cells genetically modified to express neurotrophin-3 rescue axotomized Clarke’s nucleus neurons after spinal cord hemisection in adult rats. J. Neurosci. Res. 65, 549–564.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

    Jaime Imitola

  2. Department of Neurosurgery, Brigham and Women’s Hospital and Children’s Hospital, Boston

    Yang D. Teng

  3. Harvard Medical School, Boston, MA

    Yang D. Teng

  4. Department of Biomedical Sciences, VetMed, Iowa State University, Ames, IA

    Vaclav Ourednik

  5. Department of Pediatrics, Pharmacology, and Brain, Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea

    Kook In Park

  6. Harvard Medical School and Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA

    Richard L. Sidman (Bullard Professor of Neuropathology (Neuroscience), Emeritus)

  7. Program in Developmental and Regenerative Cell Biology, The Burnham Institute, La Jolla, CA

    Evan Y. Snyder

Authors
  1. Jaime Imitola
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  2. Yang D. Teng
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  3. Vaclav Ourednik
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  4. Kook In Park
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  5. Richard L. Sidman
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  6. Evan Y. Snyder
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Editor information

Editors and Affiliations

  1. National Institute on Aging, Baltimore, MD

    Mahendra S. Rao MBBS, PhD

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© 2006 Humana Press Inc., Totowa, NJ

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Imitola, J., Teng, Y.D., Ourednik, V., Park, K.I., Sidman, R.L., Snyder, E.Y. (2006). Neural Stem Cells and Transplant Therapy. In: Rao, M.S. (eds) Neural Development and Stem Cells. Contemporary Neuroscience. Humana Press. https://doi.org/10.1385/1-59259-914-1:371

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