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Grafting of genetically manipulated swine neural system stem cells into Parkinsonian rat brain

Research Project

Project/Area Number 08671613
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionKeio University

Principal Investigator

UCHIDA Koichi  Keio University, School of Medicine, Assistant, 医学部, 助手 (00176687)

Co-Investigator(Kenkyū-buntansha) FUKUNAGA Atsushi  Keio University, School of Medicine, Assistant, 医学部, 助手 (10265829)
HARA Koichi  Keio University, School of Medicine, Assistant, 医学部, 助手 (60255479)
KAWASE Taheshi  Keio University, School of Medicine, Professor, 医学部, 教授 (40095592)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsNeural grafting / Xenograft / Parkinson's disease / Neural plate / Neural stem cell / Swine / Gene therapy / Dopamin / Neural graftig / Parkinson′s disease
Research Abstract

The purpose of this research are the evaluation of swine CNS stem cells as a substitutional donor material and investigation of the genetic availability, xenografical possibility, and neuronal circuit reconstruction of the CNS stem cells. For those examination, We made a plan to graft E17-l8 swine mesencephalic neural plate tissue into Parkinsonian rat striatum, and we observed them histologically, immunohistochemically, and electron microscopically, and eva1uated them in the respect of the recovery of amphetamine-induced rotation.
As a result, almost all graft were survived for 4-l2weeks after transplantation, treating with immunosupressants(FK506 ; 1mg/kg/day im, Endoxane ; 1Omg/kg/day ip) until 2weeks. In the result of immunohistchemical study. we found a lot of rosette formation of immature cells, swine specific neurofilament and thyrosine hydroxylase positive cells in the graft of 6weeks rat brain. In the electron microscopic study, we found swine specific neurofilament and thyrosine hydroxylase positive neural cells in the rat brain, contributing with the synaptic formation, and observed many neurofilament positive neurites with myelin.
The result suggested that E17-18 swine mesencephalic neural plate tissue should be available for xenografic transplantation. Therefore , we have made a plan of examination of grafting these cells into the Parkinsonian monkey brain, and we hope this study contribute to the development of the therapy of human Pakinson's disease in the future.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report

Research Products

(27 results)

All Other

All Publications (27 results)

  • [Publications] K.Uchida et al: "Grafting of Genetically Manipulated Cells into Adult Brain : Toward Graft-gene Therapy" Keio J Med. 45(2). 81-89 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 内田 耕一: "中枢神経系幹細胞による神経回路網再建の試み" 神経研究の進歩. 40(5). 865-873 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 内田 耕一、他: "脊髄再生への試み" LISA. 3(10). 1014-1015 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 内田 耕一、他: "神経移植による脳神経疾患の治療" 東京都医師会誌. 50(8). 1702-1705 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 内田 耕一: "神経幹細胞移植による損傷神経回路網再建の試み" 脳21. 1(1). 39-46 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Uchida et al: "Successful of grafted transgenic neural plate cells in adult central nervous system environment" The Cellular and Molecular Neurobiology. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Uchida et al: "Grafting of Genetically Manipulated Cells into Adult Brain ; Toward Graft-gene Therapy" Keio J Med. Vol.45 No.2. 81-89 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Uchida: "Reconstruction of damaged neural circuits with implantation central nervous system stem cells" Shinkei Kenkyu no Shinpo (Advances in Neurological Sciences). Vol.40, No.5. 865-873 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Uchida et al: "Trial for spinal cord regeneration" LISA. Vol.3 No.10. 1014-1015 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Uchida et al: "Neural toxicity of retroviruses" Neurosci.Lett. Vol.220. 66-68 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Hara et al: "Implantation of Xenogenic Transgenic" Cell Transplant. Vol.6, No.5. 517-519 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Hara et al: "Reconstruction of injured neurocircuit by neural stem cells" Adv.Neurotrauma.Res.Vol.8. 27-30 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Uchida: "Trial of reconstruction of damaged neural circuits with implantation of centraal nervous system stem cells" Nou21. Vol.1 No.1. 39-46 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Uchida et al: "Successful of grafted transgenic neural plate cells in adult central nervous system emvironment" The Cellular and Molecular Neurobiology. Vol.19, No.1. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] A.Fukunaga et al: "Neuropsychological evaluation and cerebralblood flow study of 30 patients with unruptured cerebral aneurysms before and after surgery" Surg.Neurol. Vol.51, No.2. 132-139 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Uchida et al: "Grafting of Genetically Manipulated Cells into Adult Brain : Toward Graft-gene Therapy" Keio J Med. 45(2). 81-89 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 内田耕一: "中枢神経系幹細胞による神経回路網再建の試み" 神経研究の進歩. 40(5). 865-873 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Uchida et al: "Neural toxicity of retroviruses" Neurosci.Lett.220. 66-68 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Uchida et al: "Transgenic neural plate contributes neuronal cells that survive greater than one year when transplanted into the adult mouse central nervous system." Experiment Neurol. 132. 194-208 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Hara et al: "Reconstruction of Injured Neurocircuit by Neural Stem Cells" Adv Neurotrauma Res. 8. 27-30 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Hara et al: "Implantation of Xenogeneic Transgenic Neural Plate Tissues into Parkinsonian Rats Brain" Cell Transplant. 6(5). 515-519 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Uchida et al: "Grafting Genetically Manipulated Cells into Adult Brain : Towaed Graft-gene Therapy" Keio J Med. 45(2). 81-89 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 内田耕一: "中枢神経系幹細胞による神経回路網再建の試み" 神経研究の進歩. 40(5). 865-873 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 内田耕一、他: "脊髄再生への試み" LISA. 3(10). 1014-1015 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Uchida et al: "Neural toxicity of retroviruses" Neurosci.Lett. 220. 66-68 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Hara et al: "Implantation of Xenigeneic Transgeneic Neural Platc Tissues into Parkinsonian Rats Brain" Cell Transplant. (Im press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Hara et al: "Reconstruction of Injured Neurocircuit by Neural Stem Cells" Adv Neurotrauma Res. (Im press). (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-03-31   Modified: 2016-04-21  

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