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of special interest. First direct evidence for long-term survival of grafted ventral mesencephalic tissue in a Parkinson's patient. An autopsy performed 18 months after transplantation showed large grafts containing TH-positive neurons and fiber out-growth into the host striatum
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of special interest Kordower JH, Freeman TB, Snow BJ, Vingerhoets FJ, Mufson EJ, Sanberg PR, Hauser RA, Smith DA, Nauert GM, Perl DP, Olanow CW. 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. 332:1995;1118-1124 First direct evidence for long-term survival of grafted ventral mesencephalic tissue in a Parkinson's patient. An autopsy performed 18 months after transplantation showed large grafts containing TH-positive neurons and fiber out-growth into the host striatum.
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Nikkhah G, Cunningham MG, McKay RDG, Björklund A. Dopaminergic microtransplants into the substantia nigra of neonatal rats with bilateral 6-OHDA lesions. II. Transplant-induced behavioral recovery. J Neurosci. 15:1995;3562-3570.
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Non-invasive dopamine determination by reversed phase HPLC in the medium of free-floating roller tube cultures of rat fetal ventral mesencephalon. A tool to assess dopaminergic tissue prior to grafting
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Studer L, Psylla M, Büchler B, Evtouchenko L, Vouga CM, Leenders KL, Seiler RW, Spenger C. Non-invasive dopamine determination by reversed phase HPLC in the medium of free-floating roller tube cultures of rat fetal ventral mesencephalon. A tool to assess dopaminergic tissue prior to grafting. Brain Res Bull. 1996;. in press.
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Studer, L.1
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Nakao N, Frodl EM, Duan WM, Widner H, Brundin P. Lazaroids improved the survival of grafted rat embryonic dopamine neurons. Proc Natl Acad Sci USA. 91:1994;12408-12412.
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Grafted cerebellar cells in a mouse model of hereditary ataxia express IGF-1 system genes and partially restore behavioral function
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of special interest. Wild-type embryonic cerebellar cells implanted into the cerebellum of adult homozygous Purkinje cell degeneration (pcd) mutant mice (a model for cerebello-olivary atrophy) assume histotypic locations, show regional IGF-1 gene expression patterns, and improve motor deficits. These results indicate the potential therapeutic value of neural transplantation in the treatment of cerebellar ataxias.
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of special interest Zhang W, Lee WH, Triarhou LC. Grafted cerebellar cells in a mouse model of hereditary ataxia express IGF-1 system genes and partially restore behavioral function. Nature Med. 2:1996;65-71 Wild-type embryonic cerebellar cells implanted into the cerebellum of adult homozygous Purkinje cell degeneration (pcd) mutant mice (a model for cerebello-olivary atrophy) assume histotypic locations, show regional IGF-1 gene expression patterns, and improve motor deficits. These results indicate the potential therapeutic value of neural transplantation in the treatment of cerebellar ataxias.
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Nature Med
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Zhang, W.1
Lee, W.H.2
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Molecular plasticity of adult Bergmann fibers is associated with radial migration of grafted Purkinje cells
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Sotelo, C.1
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The use of transplanted glial cells to reconstruct glial environments in the CNS
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Rosenberg, M.B.1
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Breakefield, X.O.6
Gage, F.H.7
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17
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0025963275
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Survival and function of intrastriatally grafted primary fibroblasts genetically modified to produce L-dopa
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Fisher LJ, Jinnah HA, Kale LC, Higgins GA, Gage FH. Survival and function of intrastriatally grafted primary fibroblasts genetically modified to produce L-dopa. Neuron. 6:1991;371-380.
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Fisher, L.J.1
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0028965223
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Somatic gene transfer of NGF to the aged brain: Behavioral and morphological amelioration
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Chen KS, Gage FH. Somatic gene transfer of NGF to the aged brain: behavioral and morphological amelioration. J Neurosci. 15:1995;2819-2825.
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Chen, K.S.1
Gage, F.H.2
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19
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0028276809
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Implanted fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevent 1-methyl-4-phenylpyridinium toxicity to dopaminergic neurons in the rat
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Frim DM, Uhler TA, Galpern WR, Beal MF, Breakefield XO, Isacson O. Implanted fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevent 1-methyl-4-phenylpyridinium toxicity to dopaminergic neurons in the rat. Proc Natl Acad Sci USA. 91:1994;5104-5108.
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Frim, D.M.1
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Beal, M.F.4
Breakefield, X.O.5
Isacson, O.6
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20
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0028953328
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Basic fibroblast growth factor increases dopaminergic graft survival and function in a rat model of Parkinsons disease
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of special interest. bFGF-expressing fibroblasts co-transplanted with embryonic day 14 (E14) ventral mesencephalon increase the number of surviving TH-positive donor cells and improve rotation behavior of 6-hydroxydopamine-lesioned recipients. These findings demonstrate that transplant survival can be enhanced by co-grafting of a growth-factor-expressing cell population.
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of special interest Takayama H, Ray J, Raymon HK, Baird A, Hogg J, Fisher LJ, Gage FH. Basic fibroblast growth factor increases dopaminergic graft survival and function in a rat model of Parkinsons disease. Nature Med. 1:1995;53-58 bFGF-expressing fibroblasts co-transplanted with embryonic day 14 (E14) ventral mesencephalon increase the number of surviving TH-positive donor cells and improve rotation behavior of 6-hydroxydopamine-lesioned recipients. These findings demonstrate that transplant survival can be enhanced by co-grafting of a growth-factor-expressing cell population.
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Nature Med
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Takayama, H.1
Ray, J.2
Raymon, H.K.3
Baird, A.4
Hogg, J.5
Fisher, L.J.6
Gage, F.H.7
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21
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0029873038
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Fibroblast growth factor-2 protects entorhinal layer II glutamatergic neurons from axotomy-induced death
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Peterson DA, Lucidi-Phillipi CA, Murphy DP, Ray J, Gage FH. Fibroblast growth factor-2 protects entorhinal layer II glutamatergic neurons from axotomy-induced death. J Neurosci. 16:1996;886-898.
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J Neurosci
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Peterson, D.A.1
Lucidi-Phillipi, C.A.2
Murphy, D.P.3
Ray, J.4
Gage, F.H.5
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22
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0029152729
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Essential role of neocortical acetylcholine in spatial memory
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of special interest. Cortical implants of acetylcholine-expressing fibroblasts ameliorate spatial memory deficits in adult rats with bilateral ibotenic-acid-induced lesions of the nucleus basalis magnocellularis. This study underscores the usefulness of genetically modified non-neural cells for functional reconstitution. Interestingly, the mere presence of acetylcholine within the neocortex appears to be sufficient for the restoration of the lesion-induced memory deficits.
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of special interest Winkler J, Suhr ST, Gage FH, Thal LJ, Fisher LJ. Essential role of neocortical acetylcholine in spatial memory. Nature. 375:1995;484-487 Cortical implants of acetylcholine-expressing fibroblasts ameliorate spatial memory deficits in adult rats with bilateral ibotenic-acid-induced lesions of the nucleus basalis magnocellularis. This study underscores the usefulness of genetically modified non-neural cells for functional reconstitution. Interestingly, the mere presence of acetylcholine within the neocortex appears to be sufficient for the restoration of the lesion-induced memory deficits.
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Nature
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Winkler, J.1
Suhr, S.T.2
Gage, F.H.3
Thal, L.J.4
Fisher, L.J.5
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23
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0027408530
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Transfer of a foreign gene into the brain using adenovirus vectors
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Akli S, Caillaud C, Vigne E, Stratford-Perricaudet L, Poenaru L, Perricaudet M, Kahn A, Peschanski MR. Transfer of a foreign gene into the brain using adenovirus vectors. Nature Genet. 3:1993;224-228.
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Nature Genet
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Akli, S.1
Caillaud, C.2
Vigne, E.3
Stratford-Perricaudet, L.4
Poenaru, L.5
Perricaudet, M.6
Kahn, A.7
Peschanski, M.R.8
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24
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0028861802
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Transplantation to the rat brain of human neural progenitors that were genetically modified using adenoviruses
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of special interest. Demonstrates the feasibility of adenovirus-mediated gene transfer into human donor cells.
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of special interest Sabaté O, Horellou P, Vigne E, Colin P, Perricaudet M, Buc-Caron MH, Mallet J. Transplantation to the rat brain of human neural progenitors that were genetically modified using adenoviruses. Nature Genet. 9:1995;256-260 Demonstrates the feasibility of adenovirus-mediated gene transfer into human donor cells.
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Nature Genet
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Sabaté, O.1
Horellou, P.2
Vigne, E.3
Colin, P.4
Perricaudet, M.5
Buc-Caron, M.H.6
Mallet, J.7
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25
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0029996147
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In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector
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of outstanding interest. Exploits karyophilic determinants of HIV proteins for retroviral gene transfer into postmitotic cells. The authors report the stable in vivo transduction of adult striatal neurons. This study might well ring in the use of HIV-based vectors for gene transfer into the adult CNS.
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of outstanding interest Naldini L, Blömer U, Gallay P, Ory D, Mulligan R, Gage FH, Verma IM, Trono D. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science. 272:1996;263-267 Exploits karyophilic determinants of HIV proteins for retroviral gene transfer into postmitotic cells. The authors report the stable in vivo transduction of adult striatal neurons. This study might well ring in the use of HIV-based vectors for gene transfer into the adult CNS.
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Science
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Naldini, L.1
Blömer, U.2
Gallay, P.3
Ory, D.4
Mulligan, R.5
Gage, F.H.6
Verma, I.M.7
Trono, D.8
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26
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0025833294
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Region-specific differentation of the hippocampal stem cell line HiB5 upon implantation into the developing mammalian brain
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Renfranz PJ, Cunningham MG, McKay RDG. Region-specific differentation of the hippocampal stem cell line HiB5 upon implantation into the developing mammalian brain. Cell. 66:1991;713-729.
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Renfranz, P.J.1
Cunningham, M.G.2
McKay, R.D.G.3
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27
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0026501444
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Multipotent neural cell lines can engraft and participate in development of mouse cerebellum
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Snyder EY, Deitcher DL, Walsh C, Arnold-Aldea S, Hartwieg EA, Cepko CL. Multipotent neural cell lines can engraft and participate in development of mouse cerebellum. Cell. 68:1992;33-51.
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Snyder, E.Y.1
Deitcher, D.L.2
Walsh, C.3
Arnold-Aldea, S.4
Hartwieg, E.A.5
Cepko, C.L.6
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28
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Target regulation of neuronal differentiation in a temperature-sensitive cell line derived from medullary raphe
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Whittemore SR, White LA. Target regulation of neuronal differentiation in a temperature-sensitive cell line derived from medullary raphe. Brain Res. 615:1993;27-40.
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Whittemore, S.R.1
White, L.A.2
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29
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0027250968
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Variable morphological differentiation of a raphe-derived neuronal cell line following transplantation into the adult rat CNS
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Onifer SM, Whittemore SR, Holets VR. Variable morphological differentiation of a raphe-derived neuronal cell line following transplantation into the adult rat CNS. Exp Neurol. 122:1993;130-142.
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Onifer, S.M.1
Whittemore, S.R.2
Holets, V.R.3
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30
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0028828510
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The adult CNS retains the potential to direct region-specific differentiation of a transplanted neuronal precursor cell line
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of outstanding interest. RN33B, a temperature-sensitive neuronal cell line derived from rat medullary raphe nucleus, acquires remarkable region-specific morphological features upon transplantation into the cortex and hippocampus of neonatal and adult rats. This regional differentiation in heterotopic areas suggests that the adult brain is able to guide the differentiation of transplanted neuronal progenitors.
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of outstanding interest Shihabuddin LS, Hertz JA, Holets VR, Whittemore SR. The adult CNS retains the potential to direct region-specific differentiation of a transplanted neuronal precursor cell line. J Neurosci. 15:1995;6666-6678 RN33B, a temperature-sensitive neuronal cell line derived from rat medullary raphe nucleus, acquires remarkable region-specific morphological features upon transplantation into the cortex and hippocampus of neonatal and adult rats. This regional differentiation in heterotopic areas suggests that the adult brain is able to guide the differentiation of transplanted neuronal progenitors.
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J Neurosci
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Shihabuddin, L.S.1
Hertz, J.A.2
Holets, V.R.3
Whittemore, S.R.4
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31
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0030007965
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Conditionally immortalized neural progenitor cells grafted to the striatum exhibit site-specific neuronal differentiation and establish connections with the host globus pallidus
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Lundberg C, Winkler C, Whittemore SR, Björklund A. Conditionally immortalized neural progenitor cells grafted to the striatum exhibit site-specific neuronal differentiation and establish connections with the host globus pallidus. Neurobiol Dis. 3:1996;33-50.
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Lundberg, C.1
Winkler, C.2
Whittemore, S.R.3
Björklund, A.4
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32
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0029123286
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CNS-derived neural progenitor cells for gene transfer of nerve growth factor to the adult rat brain: Complete rescue of axotomized cholinergic neurons after transplantation into the septum
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Martinez-Serrano A, Lundberg C, Horellou P, Fisher W, Bentlage C, Campbell K, McKay RDG, Mallet J, Björklund A. CNS-derived neural progenitor cells for gene transfer of nerve growth factor to the adult rat brain: complete rescue of axotomized cholinergic neurons after transplantation into the septum. J Neurosci. 15:1995;5668-5680.
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Martinez-Serrano, A.1
Lundberg, C.2
Horellou, P.3
Fisher, W.4
Bentlage, C.5
Campbell, K.6
McKay, R.D.G.7
Mallet, J.8
Björklund, A.9
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33
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Reversal of age-dependent cognitive impairments and cholinergic neuron atrophy by NGF-secreting neural progenitors grafted to the basal forebrain
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of special interest. The authors infected the neural precursor cell line HiB5 with a retroviral vector encoding NGF and transplanted the transduced cells to the nucleus basalis magnocellularis of learning-impaired aged rats. After transplantation, the cells sustained transgene expression for up to 10 weeks, reversing cholinergic neuron atrophy in the grafted area and improving performance in spatial memory tests.
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of special interest Martinez-Serrano A, Fischer W, Björklund A. Reversal of age-dependent cognitive impairments and cholinergic neuron atrophy by NGF-secreting neural progenitors grafted to the basal forebrain. Neuron. 15:1995;473-484 The authors infected the neural precursor cell line HiB5 with a retroviral vector encoding NGF and transplanted the transduced cells to the nucleus basalis magnocellularis of learning-impaired aged rats. After transplantation, the cells sustained transgene expression for up to 10 weeks, reversing cholinergic neuron atrophy in the grafted area and improving performance in spatial memory tests.
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(1995)
Neuron
, vol.15
, pp. 473-484
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Martinez-Serrano, A.1
Fischer, W.2
Björklund, A.3
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34
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Ex vivo gene transfer of brain-derived neurotrophic factor to the intact rat forebrain: Neurotrophic effects on cholinergic neurons
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Martinez-Serrano A, Hantzopoulos PA, Björklund A. Ex vivo gene transfer of brain-derived neurotrophic factor to the intact rat forebrain: neurotrophic effects on cholinergic neurons. Eur J Neurosci. 8:1996;727-735.
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Martinez-Serrano, A.1
Hantzopoulos, P.A.2
Björklund, A.3
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0030222250
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Autocrine BDNF secretion enhances the survival and serotonergic differentiation of raphe neuronal precursor cells granted into the adult rat CNS
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Eaton MJ, Whittemore SR. Autocrine BDNF secretion enhances the survival and serotonergic differentiation of raphe neuronal precursor cells granted into the adult rat CNS. Exp Neurol. 140:1996;105-114.
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Eaton, M.J.1
Whittemore, S.R.2
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36
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0028169809
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Neural-targeted gene therapy for rodent and primate hemiparkinsonism
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Anton R, Kordower JH, Maidment NT, Manaster JS, Kane DJ, Rabizadeh S, Schueller SB, Yang J, Rabizadeh S, Edwards RH, et al. Neural-targeted gene therapy for rodent and primate hemiparkinsonism. Exp Neurol. 127:1994;207-218.
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Anton, R.1
Kordower, J.H.2
Maidment, N.T.3
Manaster, J.S.4
Kane, D.J.5
Rabizadeh, S.6
Schueller, S.B.7
Yang, J.8
Rabizadeh, S.9
Edwards, R.H.10
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37
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0028951119
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Neural progenitor cell engraftment corrects lysosomal storage throughout the MPS VII mouse brain
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of outstanding interest. Immortalized neural precursor cells were transplanted into the ventricles of newborn mice with mucopolysaccharidosis VII, a lysosomal storage disease caused by a deficiency in β-glucuronidase. The transplanted cells populated the host brains in large numbers, and their endogenous β-glucuronidase activity decreased lysosomal storage in host neurons and glia. This experiment demonstrates how the widespread incorporation of neural donor cells can be exploited to reconstitute a deficient protein in large areas of the host brain.
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of outstanding interest Snyder EY, Taylor RM, Wolfe JH. Neural progenitor cell engraftment corrects lysosomal storage throughout the MPS VII mouse brain. Nature. 374:1995;367-370 Immortalized neural precursor cells were transplanted into the ventricles of newborn mice with mucopolysaccharidosis VII, a lysosomal storage disease caused by a deficiency in β-glucuronidase. The transplanted cells populated the host brains in large numbers, and their endogenous β-glucuronidase activity decreased lysosomal storage in host neurons and glia. This experiment demonstrates how the widespread incorporation of neural donor cells can be exploited to reconstitute a deficient protein in large areas of the host brain.
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Nature
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Snyder, E.Y.1
Taylor, R.M.2
Wolfe, J.H.3
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38
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Expression of human beta-hexosaminidase alpha-subunit gene (the gene defect of Tay-Sachs disease) in mouse brains upon engraftment of transduced progenitor cells
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Lacorazza HD, Flax JD, Snyder EY, Jendoubi M. Expression of human beta-hexosaminidase alpha-subunit gene (the gene defect of Tay-Sachs disease) in mouse brains upon engraftment of transduced progenitor cells. Nature Med. 2:1996;424-429.
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of special interest Campbell K, Olsson M, Björklund A. Regional incorporation and site-specific differentiation of striatal precursors transplanted to the embryonic forebrain ventricle. Neuron. 15:1995;1259-1273 Embryonic mouse cells from the ganglionic eminences and the ventral mesencephalon were implanted into the ventricle of embryonic rats and traced with species-specific antibodies. Cells from the lateral but not the medial ganglionic eminence were consistently detected in the host striatum. In addition, cells from all three donor populations were found incorporated in several heterotopic locations. The authors suggest that precursor cells from the lateral ganglionic eminence may be positionally specified for striatal incorporation.
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of special interest Brüstle O, Maskos U, McKay RDG. Host-guided migration allows targeted introduction of neurons into the embryonic brain. Neuron. 15:1995;1275-1285 Genetically labeled neural precursor cells derived from ventral and dorsal mouse telencephalon and injected into the telencephalic vesicles of embryonic rats incorporate equally into a variety of telencephalic, diencephalic, and mesencephalic brain regions where they acquire regional phenotypes. This study supports the idea that precursor cell migration and differentiation are predominantly regulated by non-cell-autonomous signals.
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of special interest. Investigates the role of PSA - NCAM in the migration of olfactory interneuron precursor cells using reciprocal transplantation of neonatal subventricular zone cells derived from wild-type and NCAM mutant mice. The results support the idea that PSA-positive cells serve as their own migration substrate and depict PSA as a non-cell-autonomous factor essential for cell migration in the rostral migratory stream.
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of special interest Hu H, Tomasiewicz H, Magnuson T, Rutishauser U. The role of polysialic acid in migration of olfactory bulb interneuron precursors in the subventricular zone. Neuron. 16:1996;735-743 Investigates the role of PSA - NCAM in the migration of olfactory interneuron precursor cells using reciprocal transplantation of neonatal subventricular zone cells derived from wild-type and NCAM mutant mice. The results support the idea that PSA-positive cells serve as their own migration substrate and depict PSA as a non-cell-autonomous factor essential for cell migration in the rostral migratory stream.
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(1996)
Neuron
, vol.16
, pp. 735-743
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Hu, H.1
Tomasiewicz, H.2
Magnuson, T.3
Rutishauser, U.4
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79
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0029930911
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In vivo growth factor expansion of endogenous subependymal neural precursor cell populations in the adult mouse brain
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of special interest. Infusion of EGF into the lateral ventricle of adult mice results in increased proliferation of subependymal cells, which subsequently migrate into the adjacent brain parenchyma. This observation suggests that constitutively dividing subependymal progenitors are amenable to external modulation.
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of special interest Craig CG, Tropepe V, Morshead CM, Reynolds BA, Weiss S, Van der Kooy D. In vivo growth factor expansion of endogenous subependymal neural precursor cell populations in the adult mouse brain. J Neurosci. 16:1996;2649-2658 Infusion of EGF into the lateral ventricle of adult mice results in increased proliferation of subependymal cells, which subsequently migrate into the adjacent brain parenchyma. This observation suggests that constitutively dividing subependymal progenitors are amenable to external modulation.
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(1996)
J Neurosci
, vol.16
, pp. 2649-2658
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Craig, C.G.1
Tropepe, V.2
Morshead, C.M.3
Reynolds, B.A.4
Weiss, S.5
Van der Kooy, D.6
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80
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0030448423
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Single factors direct the differentiation of stem cells from fetal and adult nervous system
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of special interest. Neural stem cells derived from the embryonic and adult rodent brain are clonally expanded under the presence of growth factors. Upon growth factor withdrawal, these stem cells differentiate with remarkable consistency into astrocytes, oligodendrocytes, and neurons. Addition of platelet-derived growth factor (PDGF), ciliary neurotrophic factor (CNTF), and triiodothyronine (T3) during growth factor withdrawal directs the stem cells specifically to neuronal, astrocytic, and oligodendroglial fates. This study demonstrates that the fate choice of self-renewing, multipotential CNS stem cells can be instructively influenced by non-cell-autonomous factors.
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of special interest Johe KK, Hazel TG, Müller T, Dugich-Djordjevic MM, McKay RDG. Single factors direct the differentiation of stem cells from fetal and adult nervous system. Genes Dev. 1996; Neural stem cells derived from the embryonic and adult rodent brain are clonally expanded under the presence of growth factors. Upon growth factor withdrawal, these stem cells differentiate with remarkable consistency into astrocytes, oligodendrocytes, and neurons. Addition of platelet-derived growth factor (PDGF), ciliary neurotrophic factor (CNTF), and triiodothyronine (T3) during growth factor withdrawal directs the stem cells specifically to neuronal, astrocytic, and oligodendroglial fates. This study demonstrates that the fate choice of self-renewing, multipotential CNS stem cells can be instructively influenced by non-cell-autonomous factors.
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(1996)
Genes Dev
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Johe, K.K.1
Hazel, T.G.2
Müller, T.3
Dugich-Djordjevic, M.M.4
McKay, R.D.G.5
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81
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0029810898
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Reversible immortalization of mammalian cells mediated by retroviral transfer and site-specific recombination
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of special interest. The authors combined retroviral gene transfer and the Cre/LoxP recombination system to design a reversible immortalization procedure. The immortalizing vector harbors Simian virus 40 large T (SV40T) placed between LoxP sites. The oncogene is later excised using Cre-expression vectors. Removal of the oncogene and reversion to a pre-immortalized stage are important steps towards a potential clinical application of immortalization strategies.
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of special interest Westerman KA, Leboulch P. Reversible immortalization of mammalian cells mediated by retroviral transfer and site-specific recombination. Proc Natl Acad Sci USA. 93:1996;8971-8976 The authors combined retroviral gene transfer and the Cre/LoxP recombination system to design a reversible immortalization procedure. The immortalizing vector harbors Simian virus 40 large T (SV40T) placed between LoxP sites. The oncogene is later excised using Cre-expression vectors. Removal of the oncogene and reversion to a pre-immortalized stage are important steps towards a potential clinical application of immortalization strategies.
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(1996)
Proc Natl Acad Sci USA
, vol.93
, pp. 8971-8976
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Westerman, K.A.1
Leboulch, P.2
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