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Induction of neuronal differentiation of stem cell or cancer cell with VHL-gene transfer and neuronal regeneration using the transferred cells

Research Project

Project/Area Number 13557120
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Cerebral neurosurgery
Research InstitutionYokohama City University

Principal Investigator

KANNO Hiroshi  Yokohama City University Graduate School of Medicine, Neurosurgery, Associate Professor, 大学院・医学研究科, 助教授 (40244496)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Isao  Yokohama City University, Neurosurgery, Professor, 大学院・医学研究科, 教授 (30158266)
NAGASHIMA Yoji  Yokohama City University, Pathology, Associate Professor, 大学院・医学研究科, 助教授 (10217995)
YAMADA Hitoshi  Yokohama City University, Neurology, Associate Professor, 医学部附属病院, 助教授 (70240033)
YAO Masahiro  Yokohama City University, Urology, Associate Professor, 大学院・医学研究科, 助教授 (00260787)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
KeywordsNeuronal regeneration / Neural progenitor cell / Neuroblastoma / VHL gene / Parkinson disease / von Hippel-Lindau病 / 神経芽細胞腫 / 脳梗塞
Research Abstract

With transductions of wild-type VHL (von Hippel-Lindau) gene, mutated-type VHL gene, and anti-sense VHL gene, we showed VHL protein had induction ability of neuronal differentiation in neural progenitor cells and neuroblastoma cells. NPCs may provide dopaminergic neurons for the treatment of Parkinson's disease (PD). However, transplantation of NPCs into the striatum by current methods has had limited success. It is possible to reverse the symptoms of PD in model rats but difficult to reverse them in humans because the number of dopaminergic neurons generated from NPCs is small (less than 1000 cells). We transduced VHL gene into NPCs isolated from embryonic rat brain. The NPCs with the trunsduced VHL gene efficiently differentiated into tyrosine hydroxylase (TH)-positive neurons in vitro. NPCs with the trunsduced VHL gene, which were labeled in advance with bromodeoxyuridine, were transplanted into the striatum of a rat model of PD. Numerous bromodeoxyuridine-TH double-labeled cells were seen close to the transplant site, showing that the transplanted cells efficiently generated new dopaminergic neurons within he host striatum. Moreover, all of the animals with NPCs with VHL showed a remarkable decrease in apomorphine-induced rotations. These findings show that NPCs with the VHL gene can efficiently generate dopaminergic neurons and that sufficient a number of dopaminergic neurons (more than 20,000 cells) can develop from to reverse the symptoms of PD in humans. VHL gene transduction provides a new therapeutic approach for treatment of PD.

Report

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

    (27 results)

All Other

All Publications (27 results)

  • [Publications] 菅野 洋: "神経幹細胞と転写因子"CLINICAL NEUROSCIENCE. 20(1). 49-52 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Murata H: "Von Hippel-Lindau tumor suppressor protein transforms human neuroblastoma cells into neuron-like cells"Cancer Research. 62(23). 7004-7011 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kanno H: "Meningioma showing VHL gene inactivation in a patient with von Hippel-Lindan disease"Neurology. 60. 1197-1199 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada H: "Transfer of the von Hippel-Lindau tumor suppressor gene to neuronal progenitor cells in treatment for Parkinson's disease."Annals of Neurology. 54(3). 352-359 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Murakami K: "Lavendustin A enhances axon elongation in VHL gene-transfected neural stem cells"NeuroReport. 15(4). 611-614 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 菅野 洋: "ホストシークエンス時代における脳腫瘍の研究と治療"九州大学出版会. 561 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Murata H, Tajima N, Nagashima Y, Yao M, Baba M, Goto M, Kawamoto S, Yamamoto I, Okuda K, Kanno H.: "Von Hippel-Lindau tumor suppressor protein transforms human neuroblastoma cells into functional neuron-like cells."Cancer Research. 62(23). 7004-7011 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada H, Dezawa M, Shimazu S, Baba M, Sawada H, Kuroiwa Y, Yamamoto I, Kanno H: "Transfer of the von Hippel-Lindau tumor suppressor gene to neuronal progenitor cells in treatment for Parkinson's disease."Annals of Neurology. 54(3). 352-359 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Murakami K, Kanno H, Yamamoto I, Saito T: "Lavendustin A enhances axon elongation in VHL-gene transferred neural l stem cells."NeuroReport. 15(4). 611-614 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 菅野 洋: "神経幹細胞と転写因子"CLINICAL NEUROSCIENCE. 20(1). 49-52 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Murata H: "Von Hippel-Lindau tumor suppressor protein transforms human neuroblastoma cells into neuron-like cells"Cancer Research. 62(23). 7004-7011 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kanno H: "Meningioma showing VHL gene inactivation in a patient with von Hippel-Lindau disease"Neurology. 60. 1197-1199 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamada H: "Transfer of the von Hippel-Lindau tumor suppressor gene to neuronal progenitor cells in treatment for Parkinson's disease"Annals of Neurology. 54(3). 352-359 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Murakami K: "Lavendustin A enhances axon elongation in VHL gene-transfected neural stem cells"NeuroReport. (発行予定). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 菅野 洋: "ホストシークエンス時代における脳腫瘍の研究と治療"九州大学出版会. 561 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 菅野 洋, 村田英俊, 林明宗, ほか3名: "弧発性および家族性血管芽腫の遺伝子診断とそれに基く治療法の選択"Neuro-Oncology. 11(2). 79-82 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 田村和朗, 内野真也, 菅野洋, ほか7名: "家族性腫瘍に対する治療法の選択"家族性腫瘍. 2(1). 6-15 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 菅野 洋: "神経幹細胞と転写因子"CLINICAL NEUROSCIENCE. 20(1). 49-52 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Murata H, Tajima N, Kanno H, ほか7名: "Von Hippel-Lindau tumor suppressor protein transforms human neuroblastoma cells into functional neuron-like cells"Cancer Research. 62(23). 7004-7011 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kanno H, Yamamoto I, ほか2名: "Meningioma showing VHL gene inactivation in a patient with von Hippel-Lindau disease"Neurology. (発行予定). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 菅野洋, 村田英俊, 後藤昌之, ほか: "ポストシークエンス時代における脳腫瘍の研究と治療"九州大学出版会. 561 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 菅野洋, 鈴木伸一, 村田英俊ほか: "下垂体腺腫におけるvon Hippel-Lindau腫瘍抑制遺伝子産物の発現"日本内分泌学会雑誌. 77(2). 103-105 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 菅野洋, 権藤学司, 村田英俊ほか: "脊髄血管芽腫の外科治療と遺伝子診断"脊髄外科. 15(3). 207-212 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Inamura Y, Nishio Y, Kanno H. et al.: "Crush and imprint cytology of subependymoma"Acta Cytol. 45(4). 636-640 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Chang CC, Kanno H, Yamamoto I, et al.: "Cere brovascular reactivity to acetogolaniide in alert patients with cerebral in farction"Nacl Med Commun. 22(10). 1119-1122 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Baba M, Hirai S, Yao M, et al.: "Tumor suppressor protein VHL is induced at high cell densitg and mediates contact inhibition of cell growth"Oncogene. 20. 2727-2736 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 菅野洋: "神経幹細胞と転写因子"CLINICAL NEUROSCIENCE. 20(1). 49-52 (2002)

    • Related Report
      2001 Annual Research Report

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

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