212 Basic Medical Sciences and Clinics 2002122 (3) : 100126325 ( 2002) 0320212207 3 ( 100083) : : ; ; :R741105 :A (central nervous system [1 CNS) ] 1998 19 20 James Thomson John Gearhart (embryonic stem cells ES cells) ; [2 3 ] (peripheral nervous system PNS) CNS CNS [4 7 CNS ] ( 1) (stem cells) CNS CNS CNS? CNS CNS 1 1992 Reynolds Richards [8 9 ] ( neural stem cells NSCs) CNS ( 1989 ) CNS ( ) CNS CNS PNS CNS :2002-03 - 06 : ( G1999054008) 3
2002122 (3) Basic Medical Sciences and Clinics 213 2 [10 ] 1 Fig 1 Produced location of embryo and adult stem cell in central nervous system of human being CNS CNS : ( subven2 tricular zone SVZ) (subgran2 CNS ular zone SGZ) [11 ] SVZ (rostral migratory stream RMS) ;SGZ (epidermal growth factor EGF) ( basic fibroblast growth factor bfgf) [12 ] [13 NSC ] ( 1) 1998 Eriksson 2 4 [16 17 ] (S ) DNA 52 (52bro2 modeoxyuridine BrdU) Br2 [18 ] ; [14 du ] Johansson (neurospheres) [8 ] 16 19 CNS ; [11 19 ] [15 ] CNS
214 Basic Medical Sciences and Clinics 2002122 (3) 50 [20 ] CNS PΠT 1 :hgfp [27 (telomerase) ] ( neuroepithelial stem cell pro2 [21 ] tein nestin) mushashi1 (leukemia inhibitory factor LIF) nestin ( EΠnestin) mushashi1 ( PΠmushashi1) LIF (htert) GFP [22 ] PΠmushashi1 : v2myc large2t hgfp EΠnestin : EGFP HNSC1100 ; 40h ; [28 ] 3 [23 24 ] Nobuko 50 ( ) CD133 + Π CNS CD34 - ΠCD45 - [25 ] CD133 + [29 ] ; 62 (62OHDA) 1 % 6 % (TGF ) CD9 [30 ] CD15 CD81 CD95(Fas) GD2 [26 I(MHC2Class2I) 2 ] 90min SGZ SVZ ( GFP) [31 GFP ( EGFP) ] Goldman GFP 1 (PΠT 1) PΠT 1 CNS
2002122 (3) Basic Medical Sciences and Clinics 215 [32 ] [36 CNS ] CNS [33 ] 98 % western blot Nurr1 CNS [37 ] 4 CNS CNS CNS CNS PD 20 (Parkinson s disease PD) (Alzheimer s disease AD) (Huntington s disease HD) CNS PD [39 ] [40 ] PD [34 ] PD PD [39 ] CNS PD ; [37 IL2 ] 1 IL21 ( tyrosine 1999 Janet Fricker hydroxylase) (dopamine DA) (do2 Cedars2Sinai pa2decarboxylase DDC) (DA transport2 PD [38 ] PD er DAT) PD 2 IL2 1 IL211 ( Glail2derived neuro2 6 8 trophic factor GDNF) LIF Fluoro2DOPA PET [41 ] 20 % 25 % [35 ]
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218 Basic Medical Sciences and Clinics 2002122 (3) 388. [39 ] Svendsen CN Caldwell MA Shen J et al. Long2term surviv2 al of human central nervous system progenitor cells transplanted into a rat model of Parkinson s disease [J ]. Exp Neurol 1997 148 : 135-146. [40 ] Nishino H Hida H Takei N et al. Mesencephalic neural stem (progenitor) cells develop to dopaminergic neurons more strongly in dopamine2depleted striatum than in intact striatum [J ]. Exp Neurol 2000 164 : 209-214. [41 ] Fricker J. Human neural stem cells on trial for Parkinson s disease[j ]. Mol Med Today 1999 5 : 144. [42 ] Toda H Takahashi J Iwakami N et al. Grafting neural stem cells improved the impaired spatial recognition in ischemic rats [J ]. Neurosci Letters 2001 316 : 9-12. [43 ] Benedetti S Piroia B Pollo B. Gene therapy of experimental brain tumors using neural progenitor cells [J ]. Nature Medi2 cine 2000 6 : 447-450. [44 ] Aboody KS Brown A Raioov NG et at. From the cover : neural stem cells display extensive tropism for pathology in adult brain : evidence from intracranial gliomas[j ]. Proc Natl Acad Sci USA 2000 97 : 12846-12851. [45 ] Pincus DW Goodman RR Fraser RAR et al. Neural stem and progenitor cells : a strategy for gene therapy and brain re2 pair[j ]. Neurosurgery 1998 42 : 858-867. [46 ] Kalyani AJ Rao MS. Cell lineage in the developing neural tube[j ]. Biochem Cell Biol 1998 76 : 1051-1068. Progress in neural stem cells WANG Xuan WANG Kun WANG Xiao2min (Neuroscience Research Institute Peking University Beijing 100083 China) Abstract : Recently the research methods for stem cells from central nervous system and the clinical application have at2 tracted attention of CNS study. In this review the finding of neural stem cells new research techniques and therapeutic effects on the CNS disorders such as neurodegeneration diseases ischema injury and tumors by applying neural stem cells are introduced. Key words : neural stem cells ; neuroregeneration ; cell transplantation ( 211 ) The gene therapy of central nervous system disorders ZHANG Wang2ming NIU Dong2bin XU Ru2xiang et al (Neuroscience Research Institute Peking University Beijing 100083 China) Abstract : Gene therapy is a potential and new methods of treating many neurological diseases that were considered re2 fractory to current conventional treatments. By injection of viral vectors or transplantation of genetically engineered cells into specific sites of the brain the development of technologies for delivery of foreign genes into brain opened the field to promising treatments for CNS disorders. But the development of gene therapy for neurological diseases represents a more complex problem than that for other systemic disorders. Incomplete characterization of target organs ( brain and spinal cord) and additional challenges such as post2mitotic cells heterogeneity of cell types and circuits and limited access all contribute to the difficulties. For this reason this report provides an update outline of gene therapy in CNS and re2 views current researches in this filed. Key words : gene therapy ; central nervous system ; viral vectors Corresponding author : Wang Xiao2min