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Transplantation of monkey ES cell-derived dopaminergic neurons into the brain of MPTP-treated monkey

Research Project

Project/Area Number 14370431
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

TAKAHASHI Jun  Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (10270779)

Co-Investigator(Kenkyū-buntansha) NAKATSUJI Norio  Kyoto University, Institute for Frontier Medical Sciences, Professor, 再生医科学研究所, 教授 (80237312)
SASAI Yoshiki  RIKEN, Center for Developmental Biology, Group Director, 理化学研究所・CDB, グループディレクター (20283616)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2004: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 2003: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsES cell / Cell Transplantation / Parkinson's disease / Dopaminergic neuron / ドーパミン産生ニューロン / ドーパミン作動性ニューロン
Research Abstract

Parkinson's disease is a neurodegenerative disorder characterized by loss of midbrain dopaminergic (DA) neurons. ES cells are currently the most promising donor cell source for cell-replacement therapy of Parkinson's disease. We previously described a strong neuralizing activity present on the surface of stromal cells, named SDIA (stromal cell-derived inducing activity). In this study, we generated neurospheres composed of neural progenitors from monkey ES cells, which are capable of producing large numbers of DA neurons. We demonstrated that FGF20, preferentially expressed in the substantia nigra, acted synergistically with FGF2 to increase the number of DA neurons in ES cell-derived neurospheres. We also analyzed the effect of transplantation of DA neurons generated from monkey ES cells into 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, a primate model for Parkinson's disease. Behavioral studies and functional imaging revealed that the transplanted cells functioned as DA neurons and attenuated MPTP-induced neurological symptoms.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (11 results)

All 2005 2004 Other

All Journal Article (8 results) Publications (3 results)

  • [Journal Article] Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model.2005

    • Author(s)
      Takagi Y, et al.
    • Journal Title

      Journal fo Clinical Investigation 115

      Pages: 102-109

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Estrogen promotes the differentiation and survival of dopaminergic neurons derived from human neural stem cells.2005

    • Author(s)
      Kishi Y, et al.
    • Journal Title

      Journal of Neuroscience Research 79

      Pages: 279-286

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model.2005

    • Author(s)
      Takagi Y, Takahashi J, Saiki H, Morizane A, Hayashi T, Kishi Y, Hukuda H, Okamoto Y, Koyanagi M, Ideguchi M, Hayashi H, Imazato T, Kawasaki H, Suemori H, Omachi S, Iida H, Itoh N, Nakatsuji N, Sasai Y, Hashimoto N.
    • Journal Title

      J Clin Invest. 115

      Pages: 102-109

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Estrogen promotes the differentiation and survival of dopaminergic neurons derived from human neural stem cells.2005

    • Author(s)
      Kishi Y, Takahashi J, Koyanagi M, Morizane A, Okamoto Y, Horiguchi S, Tashiro K, Honjo T, Fujii S, Hashimoto
    • Journal Title

      J Neurosci Res. 79

      Pages: 279-286

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model2005

    • Author(s)
      Takagi Y, et al.
    • Journal Title

      J.Clin.Invest. 115・1

      Pages: 102-109

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Estrogen promotes the differentiation and survival of dopaminergic neurons derived from human neural stem cells2005

    • Author(s)
      Kishi Y, et al.
    • Journal Title

      J.Neurosci.Res. 79・3

      Pages: 279-286

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Neural precursor cells derived from human embryonic brain retain regional specificity.2004

    • Author(s)
      Horiguchi et al.
    • Journal Title

      Journal of Neuroscience Research 75

      Pages: 817-824

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Neural precursor cells derived from human embryonic brain retain regional specificity.2004

    • Author(s)
      Horiguchi S, Takahashi J, Kishi Y, Morizane A, Okamoto Y, Koyanagi M, Tsuji M, Tashiro K, Honjo T, Fujii S, Hashimoto N.
    • Journal Title

      J Neurosci Res. 75(6)

      Pages: 817-824

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Horiguchi S, et al.: "Neural precursor cells derived from human embryonic brain retain regional specificity"J.Neurosci.Res.. 75・6. 817-824 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Toda H, et al.: "Stem cell-derived neural stein/progenitor cell supporting factor (SDNSF) is an autocrine/paracrine survival factor for neural stem cells"J.Biol.Chem.. 278・32. 35491-35500 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Morizane A et al.: "Optimal conditions for in vivo induction of dopaminergic neurons from ES cells through stromal cell-derived inducing activity"J Neurosci Res. 69・6. 934-939 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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