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Generation of human neural stem cell lines and brain models of hypoxic-ischemic brain damage

Research Project

Project/Area Number 13670834
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionDokkyo University School of Medicine

Principal Investigator

EGUCHI Mitsuoki (2003)  Dokkyo University School of Medicine, Department of Pediatrics, Professor, 医学部, 教授 (60020799)

中川 栄二 (2001-2002)  獨協医科大学, 医学部, 講師 (70333002)

Co-Investigator(Kenkyū-buntansha) YAMANOUCHI Hideo  Dokkyo University School of Medicine, Department of Pediatrics, Associate Professor, 医学部, 助教授 (10250226)
NAKAGAWA Eiji  National Institute of Neuroscience, National Center of Neurology and Psychiatry, Department of Mental Retardation and Birth Defect Research, Research fellow, 神経研究所・疾病研究第2部, 研究員 (70333002)
江口 光興  獨協医科大学, 医学部, 教授 (60020799)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordshuman neural stem cells / human neural crest stem cells / neuronal cell death / hyoxic-ischemic brain damage / epilepsy / hippocampus / ヒト神経堤幹細胞 / 神経幹細胞移植 / カイニン酸
Research Abstract

We have generated self-renewing and multipotent human neural stem cells (NSCs) via retrovirus-mediated v-myc transfer into embryonic human brain cells, and have isolated several clonal cell lines. These lines can be maintained in an undifferentiated state, or induced to differentiate by changing the culture conditions. One of these cell lines, HB1/C4, is genetically modified NSCs maintained as a stable cell line in serum-free medium remains uncommited, undifferentiated, multipotent and express phenotypes specific for NSCs such as nestin, musashi and vimentin.
When NB1/C4 cells were grown in a serum containing medium (5% fetal bovine serum and 5% equine serum), several differentiated cell types, which are known as progeny of NSCs such as neurons, astrocytes and oligodendrocytes were induced in culture.
To investigate the fate of HB1/C4 cells in a myelin deficiency structure, we grafted NB1/C4 cells into the brain of adult or neonatal myelin mutant shiverer mouse. HB1/C4 cells were found to migrate extensively from the site of implantation into other anatomical sites and to remyelinate formerly unmyelinated axons. The ability of the HB1/C4 cells, human immortalized NSCs, to respond in vitro to guidance cues and signals that can direct their differentiation along multiple phenotypic pathways suggests that they can providea powerful and virtually unlimitted source of cells for gene cell therapy in the human neurological diseases.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Nagai A, Nakagawa E, Choi H.B, Hatori K, Kobayashi S, Kim SU.: "Erythropoietin and erythropoietin receptors in human CNS neurons, astrocytes, microglia and oligodendrocytes grown in culture."J.Neuropath.Exp.Neur.. 60. 386-392 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nagai A, Nakagawa E, Hatori K, Choi HB, McLarnon JG, Lee MA, Kim SU.: "Generation and characterization of immortalized human microglial cell lines : expression of cytokines and chemokines."Neurobiol Dis.. 8(6). 1057-1068 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Yamanouchi, T.Ota, G.Imataka, E.Nakagawa, M.Eguchi: "Reversible altered consciousness with brain atrophy by valproic acid"Pediatric Neurology. 28(5). 382-384 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideo Yamanouchi, Takako Ota, George Imataka, Yuri Hagiwara, Eiji Nakagawa, Mitsuoki Eguchi: "Congenital bilateral perisylvian syndrome associated congenital constriction band syndrome."J Child Neurol. 17. 448-450 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakagawa E, Hatori K, Nagai A, Choi HB, Jae KR.: "Generation, characterisation and brain transplantation of immortalized human neural crest stem cells. In : Zigova T, Snyder EY, Sanberg PR, eds.Neural stem cells for brain and spinal cord repair."Totowa, NJ : Humana Press. 89-106 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kim SU, Nakagawa E, Hatori K, Nagai A, Jae KR.: "Production of immortalized human neural crest stem cells. (Zigova T, Sanchez-Ramos J, eds.)"Totowa, NJ: Humana Press. 55-65 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nagai A, Nakaga E, Choi H.B, Hatori K, Kobayashi S, Kim SU.: "Erythropoietm and erythropoietin receptors in human CNS neurons, astrocytes, microglia and oligodendrocytes grown in culture."J.Neuropath.ExNeur.. 60. 386-392 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nagai A, Nakagawa E, Hatori K, Choi HB, McLarnon JG, Lee MA, Kim SU.: "Generation and characterization of immortalized human microglial cell lines : expression of cytokines and chemokines."Neurobiol.Dis.. 8(6). 1057-1068 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kim SU, Nakagawa E Hatori K, Nagai A, Jae KR.: "Production of immortalized human neural crest stem cells."Neural stem cells : methods and protocols.(Zigova T, Sanchez-Ramos J, eds)(Totowa, NJ : Humana Press). 55-65 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideo Yamanouchi, Takako Ota, George Imataka, Yuri Hagiwara, Eiji Nakagawa, Mitsuoki Eguchi.: "Congenital bilateral perisylvian syndrome associated congenital constriction band syndrome."J Child Neurol. 17. 448-450 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakagawa E, Hatori K, Nagai A, Choi HB, Jae KR.: "Generation, characterisation and brain transplantation of immortalized human neural crest stem cells."Neural stem cells for brain and spinal cord repair.(Zigova T, Snyder EM Sanberg PR, eds)(Totowa, NJ : Humana Press). 89-106 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideo Yamanouchi, Takako Ota, George Imataka, Eiii Nakagawa, Mitsuoki Eguchi: "Reversible altered consciousness with brain atrophy by valproic acid"Pediatric Neurology. 28(5). 382-384 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中川栄二, 花岡 繁: "乳児テタニーの一例"小児科診療. 66(5). 149-152 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中川栄二, 川上敏幸, 萩原ゆり, 山内秀雄, 海野健, 江口光興: "高CK血症を呈した転換性障害の一女子例"総合臨床. 52(9). 2678-2680 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Yamanouchi, T.Ota, G.Imataka, E.Nakagawa, M.Eguchi: "Reversible altered consciousness with brain atrophy by valproic acid"Pediatric Neurology. 28(5). 382-384 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中川栄二, 山内秀雄, 江口光興: "けいれん重積をきたした泣き入りひきつけの一例"小児科. 44(12). 2005-2008 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中川栄二, 奥谷真由子, 萩原ゆり, 山内秀雄, 江口光興: "インターフェロンβ-1bが寛解維持に有効であった小児多発性硬化症の一例"小児科. 44(9). 1434-1438 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中川栄二, 山脇 保, 服部政憲: "全内臓逆位および完全大血管転換を伴った18番染色体短腕欠失症候群の一例"小児科診療. 66(9). 1617-1620 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakagawa E, Hatori K, Nagai A, Choi NB, Jae KR.: "Generation, characterisation and brain transplantation of immortalized human neural crest stem cells. In : Zigova T, Snyder EY, Sanberg PR., eds. Neural stem cells for brain and spinal cord repair."Totowa, NJ : Humana Press. 89-106 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中川栄二: "神経幹細胞のソース ヒト神経幹細胞の樹立"Clinical Neuroscience. 20巻1号. 34-36 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kim SU, Nakagawa Eiji, et al.: "ToTowa, NJ : Humana Press"Production of immortalized human neurol crest stem cells 「Neurol stem cells : methods and protocols」. 55-65 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakagawa Eiji et al.: "ToTowa, NJ : Humana Press"Generation, characterization and brain transplantation of immortalized human neural crest stem cells 「Neurol stem cells for brain and spinal cord repair」. 434(89-106) (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中川 栄二: "ヒト神経幹細胞の樹立"CLINICAL NEUROSCIENCE. 20. 34-36 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nagai A., Nakagawa E, et al.: "Erythropoietin and erythropoietin receptors in human CNS neurons, astrocytes, microglia and oligodendrocytes grown in culture."J. Neuropath. Exp. Neur.. 60. 386-392 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nagai A, Nakagawa E, et al.: "Generation and characterization of immortalized human microglia cell lines expression of cytokines and chemokines."Neurobiol. Dis.. 8(6). 1057-1068 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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