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Induction of dopaminergic neurons from human ES cells, and transplantation of the cells into monkey Parkinson's disease models

Research Project

Project/Area Number 17390397
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, Institute for Frontier Medical Sciences, associate professor (10270779)

Co-Investigator(Kenkyū-buntansha) NAKATSUJI Norio  KYOTO UNIVERSITYKYOTO UNIVERSITY, Institute for Frontier Medical Scienoes, professor (80237312)
SASAI Yoshiki  Riken Kobe Institute, CDB, Group Director (20283616)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥16,750,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2007: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2006: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2005: ¥5,600,000 (Direct Cost: ¥5,600,000)
Keywordsembryonic stem cells / neural induction / cell transplantation / Parkinson's disease / dopaminergic neuron / tumor formation / ヒトES細胞 / 神経細胞移植
Research Abstract

We induced dopaminergic neurons from human ES cell lines, KhES-1, -2 -3, which were established in Kyoto University, Japan-When we grafted human ES cell-derived neural progenitors into the striatum of monkey Parkinson's disease, one of the three monkeys showed tumor formation. PET scan demonstrated an increase of glucose metabolism and an uptake of fluorothimidine at the tumor region. Immunofluorescence study showed accumulation of Oct3/4-, ES cell marker positive cells in the tumor. In to analysis of the grafted cells revealed that the cells which caused tumor formation contained Oct3/4-positive ES cells, but that the cells which did not tumors contained no such cells. These results suggest that contaminated ES cells in the graft lead to tumor formation.
This possibility was confirmed by using mouse ES cells. When ES cell-derived neural progenitor cells (NPCs) were selected. by fluorescence-activated cell sorting (FACS), these cells never famed any tumors in the mouse brain or subcutaneous space of immunodeficient mice.
These results indicate that purification of NPCs is important for the safe and effective cell transplantation, and we are now developing the method to sort out human ES cell-derived NPCs.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (42 results)

All 2008 2007 2006 2005 Other

All Journal Article (12 results) (of which Peer Reviewed: 7 results) Presentation (29 results) Book (1 results)

  • [Journal Article] Meningeal cells induce dopaminergic neurons from embryonic stem cells.2008

    • Author(s)
      Hayashi H, Morizane A, Koyanagi M, Ono Y, Sasai Y, Hashimoto N, Takahashi J.
    • Journal Title

      Eur J Neurosci 27

      Pages: 261-268

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Inhibition of the Rho/ROCK pathway reduces apoptosis during transplantation of embryonic stem cell-derived neural precursors.2008

    • Author(s)
      Koyanagi M, Takahashi J, Arakawa Y, Doi D, Fukuda H, Hayashi H, Narumiya S, Hashimoto N.
    • Journal Title

      J Neurosci Res 86

      Pages: 270-280

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Meningeal cells induce dopaminergic neurons from embryonic stem cells2008

    • Author(s)
      Hayashi, H., Morizane, A., Koyanagi, M., Ono, Y., Sasai, Y., Hashimoto, N., Takahashi, J
    • Journal Title

      Eur J Neurosci 27

      Pages: 261-268

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Inhibition of the Rho/ROCK pathway reduces apoptosis during transplantation of embryonic stem cell-derived neural precursors2008

    • Author(s)
      Koyanagi, M., Takahashi, J., Arakawa, Y., Doi, D., Fukuda, H., Hayashi, H., Narumiya, S., Hashimoto, N
    • Journal Title

      J Neurosci Res 86

      Pages: 270-280

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Meningeal cells induce dopaminergic neurons from embryonic stem cells2008

    • Author(s)
      Hayashi H, et. al.
    • Journal Title

      Eur. J. Neurosci. 27

      Pages: 261-268

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A ROCK inhibitor permits survival of dissociated human embryonic stem cells2007

    • Author(s)
      Watanabe H, et. al.
    • Journal Title

      Nature Biotech. 25

      Pages: 681-686

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of graftable progenitors of dopaminergic neurons from mouse ES cells by a combination of co-culture and neurosphere methods.2006

    • Author(s)
      Morizane A, Takahashi J, Shinoyama M, Ideguchi M, Takagi Y, Fukuda H, Koyanagi M, Sasai Y, Hashimoto N.
    • Journal Title

      J Neurosci Res. 83

      Pages: 1015-1027

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] FACS-based purification of ES cell-derived neural precursors averts tumor formation after transplantation.2006

    • Author(s)
      Fukuda H, Takahashi J, Watanabe K, Hayashi H, Morizane A, Koyanagi M, Sasai Y, Hashimoto N.
    • Journal Title

      Stem Cells 24

      Pages: 763-771

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Generation of graftable progenitors of dopaminergic neurons from mouse ES cells by a combination of co-culture and neurosphere methods2006

    • Author(s)
      Morizane, A., Takahashi, J., Shinoyama, M., Ideguchi, M., Takagi, Y., Fukuda, H., Koyanagi, M., Sasai, Y., Hashimoto, N
    • Journal Title

      J Neurosci Res 83

      Pages: 1015-1027

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] FACS-based purification of ES cell-derived neural precursors averts tumor formation after transplantation2006

    • Author(s)
      Fukuda, H., Takahashi, J., Watanabe, K., Hayashi, H., Morizane, A., Koyanagi, M., Sasai, Y., Hashimoto, N
    • Journal Title

      Stem Cells 24

      Pages: 763-771

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Immune or inflammatory response by the host brain suppresses neuronal differentiation of transplanted ES cell-derived neural precursor cells

    • Author(s)
      Ideguchi M, Shinoyama M, Gomi M, Hayashi H, Hashimoto N, Takahashi J.
    • Journal Title

      J Neurosci Res (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Immune or inflammatory response by the host brain suppresses neuronal differentiation of transplanted ES cell-derived neural precursor cells

    • Author(s)
      Ideguchi, M., Shinoyama, M., Gomi, M., Hayashi, H., Hashimoto, N., Takahashi, J
    • Journal Title

      J Neurosci Res (In press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The roles of extracellular matrices and secreting factors of PA6 in SDIA2007

    • Author(s)
      Hayashi H, et. al.
    • Organizer
      Annual meeting of Society for Neuroscience
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2007-11-04
    • Related Report
      2007 Annual Research Report
  • [Presentation] ES細胞利用によるパーキンソン病治療法の開発2007

    • Author(s)
      高橋 淳
    • Organizer
      第22回神経組織の成長・再生・移植研究会
    • Place of Presentation
      岡山
    • Year and Date
      2007-05-26
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ES cell transplantation for the treatment of Parkinson's disease2007

    • Author(s)
      Jun, Takahashi
    • Organizer
      The 22nd Annual Meeting of the Japanese Society for Neural Growth, Regeneration and Transplantation
    • Place of Presentation
      Okayama, Japan
    • Year and Date
      2007-05-26
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ES細胞移植によるパーキンソン病治療法の開発2007

    • Author(s)
      高橋 淳
    • Organizer
      第6回日本再生医療学会総会
    • Place of Presentation
      横浜
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ES細胞移植によるパーキンソン病治療法の開発2007

    • Author(s)
      高橋 淳
    • Organizer
      第27回日本医学会総会
    • Place of Presentation
      大阪
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ES細胞を用いた神経再生医療2007

    • Author(s)
      高橋 淳
    • Organizer
      第54回日本麻酔科学会学術集会
    • Place of Presentation
      札幌
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Graft's behavior and host response in cell transplantation2007

    • Author(s)
      高橋 淳
    • Organizer
      Nobel Conference on"Development and Engineering of Dopamine Neurons: From Genes to Therapy"
    • Place of Presentation
      Stockholm
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ES cell transplantation for the treatment of Parkinson's disease2007

    • Author(s)
      高橋 淳
    • Organizer
      BioKorea 2007
    • Place of Presentation
      Seoul,
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] In vivo functional studies in primates2007

    • Author(s)
      高橋 淳
    • Organizer
      Cold Spring Harbor Conference on Cell Transplantation as a Therapy for Parkinson's disease
    • Place of Presentation
      New York
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ES cell transplantation for the treatment of Parkinson's disease2007

    • Author(s)
      Jun, Takahashi
    • Organizer
      The 27th General Assembly of the Japan Medical Congress
    • Place of Presentation
      Osaka, Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Neuro-regenerative Medicine by ES cells2007

    • Author(s)
      Jun, Takahashi
    • Organizer
      The 54th Annual Meeting of the Japanese Society of Anesthesiologists
    • Place of Presentation
      Sapporo, Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Graft's behavior and host response in cell transplantation2007

    • Author(s)
      Jun, Takahashi
    • Organizer
      Nobel Conference on "Development and Engineering of Dopamine Neurons : From Genes to Therapy"
    • Place of Presentation
      Stockholm, Sweden
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ES cell transplantation for the treatment of Parkinson's disease2007

    • Author(s)
      Jun, Takahashi
    • Organizer
      BioKorea 2007
    • Place of Presentation
      Seoul, Korea
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] In vivo functional studies in primates2007

    • Author(s)
      Jun, Takahashi
    • Organizer
      Cold Spring Harbor Conference on Cell Transplantation as a Therapy for Parkinson's disease
    • Place of Presentation
      New York, U.S.A
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ES細胞を用いた神経再生医療2006

    • Author(s)
      高橋 淳
    • Organizer
      第9回日本組織工学会シンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2006-09-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Neuro-regenerative Medicine by ES cells2006

    • Author(s)
      Jut, Takahashi
    • Organizer
      The 9th Annual Meeting of the Japanese Society for Tissue Engineering
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2006-09-08
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Neuromodulation for the treatment of Parkinson's disease2006

    • Author(s)
      高橋 淳
    • Organizer
      第29回日本神経科学大会シンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2006-07-19
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Neuromodulation for the treatment of Parkinson's disease2006

    • Author(s)
      Jun, Takahashi
    • Organizer
      The 29th Annual Meeting of the Japan Neuroscience Society
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2006-07-19
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ES cell transplantation for the treatment of Parkinson's disease2006

    • Author(s)
      Jun, Takahashi
    • Organizer
      The 6th Annual Meeting of the Japan Society for Regenerative Medicine
    • Place of Presentation
      Yokohama, Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] パーキンソン病に対するES細胞移植療法の開発2005

    • Author(s)
      高橋 淳
    • Organizer
      第64回日本脳神経外科学会総会シンポジウム
    • Place of Presentation
      横浜
    • Year and Date
      2005-10-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ES cell transplantation for the treatment of Parkinson's disease2005

    • Author(s)
      Jun, Takahashi
    • Organizer
      The 64th Annual Meeting of the Japan Neurosurgical Society
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2005-10-06
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 幹細胞移植による再生医療2005

    • Author(s)
      高橋 淳
    • Organizer
      第24回日本老年医学会総会Aging Science Forum
    • Place of Presentation
      東京
    • Year and Date
      2005-06-16
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Regenerative Medicine by Stem Cells2005

    • Author(s)
      Jun, Takahashi
    • Organizer
      The 24th Annual Meeting of the Japan Geriatrics Society
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2005-06-16
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 霊長類ES細胞からのドパミン産生神経誘導と霊長類モデルへの移植後の解析2005

    • Author(s)
      高橋 淳
    • Organizer
      第25回日本脳神経外科コングレスランチョンセミナー
    • Place of Presentation
      小倉
    • Year and Date
      2005-05-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Transplantation of primate ES cell-derived dopaminergic neurons2005

    • Author(s)
      Jun, Takahashi
    • Organizer
      The 25th Annual Meeting of the Japanese Congress of Neurosurgical Surgeons
    • Place of Presentation
      Kokura, Japan
    • Year and Date
      2005-05-13
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Induction of dopaminergic neurons from ES cells and their transplantation2005

    • Author(s)
      Jun, Takahashi
    • Organizer
      The 4th Annual Meeting of the Japan Society for Regenerative Medicine
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2005-05-01
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ES細胞からのドパミン産生神経誘導と移植条件の至適化2005

    • Author(s)
      高橋 淳
    • Organizer
      第4回日本再生医療学会ワークショップ
    • Place of Presentation
      大阪
    • Year and Date
      2005-03-01
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ES細胞からのドパミン神経誘導と移植条件の至適化2005

    • Author(s)
      高橋 淳
    • Organizer
      第44回日本定位・機能神経外科学会シンポジウム
    • Place of Presentation
      大阪
    • Year and Date
      2005-01-22
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Induction of dopaminergic neurons from ES cells and their transplantation2005

    • Author(s)
      Jun, Takahashi
    • Organizer
      The 44th Annual Meeting of the Japan Society for Stereotactic and Functional Neurosurgery
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2005-01-22
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Stem Cells in Reproduction and in the Brain2006

    • Author(s)
      Takahashi J.
    • Publisher
      Springer
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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