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Improving safety in neural celltransplantation with human inducedpluripotent stem cells

Research Project

Project/Area Number 21591837
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MORIZANE Asuka  京都大学, ips細胞研究所, 特定研究員 (10528730)

Co-Investigator(Renkei-kenkyūsha) TAKAHASHI Jun  京都大学, 再生医科学研究所・ips細胞研究所, 准教授 (10270779)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsパーキンソン病 / 腫瘍化 / 神経 / 多能性幹細胞 / ソーティング / ドーパミン / 移植 / iPS細胞 / 分化誘導 / ドーパミン神経 / 神経幹細胞 / 細胞移植 / 低分子化合物
Research Abstract

We found and reported several strategies for improving safety foriPSC-derived neurons as donor cells : the usage of two small molecules for inhibiting BMPand Activin cascade, prolonged culture for differentiation and inhibition of Notchsignals in vitro before transplantation. After differentiation of the donor cells withthese methods, a good graft survival of iPSC-derived dopaminergic neurons was observedin the brain of a primate model of Parkinson' sdisease. We demonstrated that the humaniPSCs established with episomal vectors having no genomic insertion of transgenescould generate dopaminergic neurons as well as original retrovirally establishediPSCs or embryonic stem cells.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (50 results)

All 2012 2011 2010 2009 Other

All Journal Article (17 results) (of which Peer Reviewed: 9 results) Presentation (23 results) Book (2 results) Remarks (4 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 4 results)

  • [Journal Article] パーンソン病に対するiPS細胞技術の挑戦2012

    • Author(s)
      森実飛鳥. 、高橋淳
    • Journal Title

      BRAIN and NERVE

      Volume: 64巻 Pages: 29-37

    • URL

      http://ej.islib.ejournal/1416101097.html?

    • Related Report
      2011 Final Research Report
  • [Journal Article] パーキンソン病に対するiPS細胞技術の挑戦2012

    • Author(s)
      森実飛鳥、高橋淳
    • Journal Title

      BRAIN and NERVE

      Volume: 64 Pages: 29-37

    • Related Report
      2011 Annual Research Report
  • [Journal Article] urvival of human induced pluripotent stem cell-Derived midbrain dopaminergicneurons in the brain of a primate Model of Parkinson's disease2011

    • Author(s)
      Kikuchi T, Morizane A, Doi D, et al.
    • Journal Title

      Journal of Parkinson's Disease

      Volume: Vol.1 Pages: 395-412

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] A more efficient method to generate integration-free human iPS cells2011

    • Author(s)
      Okita, K., et al
    • Journal Title

      Nature Methods

      Volume: 8 Issue: 5 Pages: 409-412

    • DOI

      10.1038/nmeth.1591

    • NAID

      120002949763

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Small-molecule inhibitors of bone morphogenic protein and activin/nodal signals promote highly efficient neural induction from human pluripotent stem cells2011

    • Author(s)
      Morizane A, Doi D, Kikuchi T, Nishimura K, Takahashi J.
    • Journal Title

      J Neurosci Res

      Volume: 89(2) Issue: 2 Pages: 117-26

    • DOI

      10.1002/jnr.22547

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Survival of Human Induced Pluripotent Stem Cell--Derived Midbrain Dopaminergic Neurons in the Brain of a Primate Model of Parkinson's Disease2011

    • Author(s)
      Kikuchi T, Morizane A, Doi D, et al
    • Journal Title

      Journal of Parkinson's Disease

      Volume: 1 Issue: 4 Pages: 395-412

    • DOI

      10.3233/jpd-2011-11070

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Small Molecule Inhibitors of BMP and Activin/Nodal Signals Promote Highly Efficient Neural Induction from Human Pluripotent Stem Cells.2011

    • Author(s)
      Morizane A, Doi D, Kikuchi T, et al.
    • Journal Title

      Journal of Neuroscience Research

      Volume: 89 Pages: 117-126

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A simple method for large-scale generation of dopamine neurons from human embryonic stem cells2010

    • Author(s)
      Morizane A, Darsalia V, Guloglu MO et al.
    • Journal Title

      J Neurosci Res

      Volume: Vol.88 Issue: 16 Pages: 3467-3478

    • DOI

      10.1002/jnr.22515

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Risks and mechanisms of ontological disease following stem cell transplantation2010

    • Author(s)
      Anisimov SV, Morizane A and Correia AS
    • Journal Title

      Stem Cell Rev

      Volume: Vol.6 Issue: 3 Pages: 411-24

    • DOI

      10.1007/s12015-010-9134-5

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] ES細胞、 ips細胞を用いた細胞移植治療の臨床応用2010

    • Author(s)
      森実飛鳥、高橋淳
    • Journal Title

      月刊バイオインダストリー

      Volume: 28巻 Pages: 102-107

    • URL

      http://www.cmcbooks.co.jp/products/detail.php?product_id=3393

    • Related Report
      2011 Final Research Report
  • [Journal Article] A simple method for large-scale generation of dopamine neurons from human embryonic stem cells2010

    • Author(s)
      Morizane A, Darsalia V, Guloglu MO, et al.
    • Journal Title

      Journal of Neuroscience Research

      Volume: 88 Pages: 3467-3478

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ES細胞、iPS細胞を用いた細胞移植治療の臨床応用2010

    • Author(s)
      森実飛鳥、高橋淳
    • Journal Title

      月刊バイオインダストリー 28

      Pages: 102-107

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Risks and Mechanisms of Oncological Disease Following Stem Cell Transplantation2010

    • Author(s)
      Sergey V.Anisimov, Asuka Morizane, Ana S.Correia
    • Journal Title

      Stem Cell Review and Report Epub

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] パーキンソン病の再生医療~ES細胞、 ips細胞を用いた細胞移植治療の展望~2009

    • Author(s)
      森実飛鳥、高橋淳
    • Journal Title

      綜合臨床

      Volume: 58巻 Pages: 50-55

    • URL

      http://www.nagaishoten.co.jp/search/sogo/A200901.html

    • Related Report
      2011 Final Research Report
  • [Journal Article] パーキンソン病に対する細胞移植治療~現在の到達点と今後の課題~2009

    • Author(s)
      森実飛鳥、高橋淳
    • Journal Title

      実験医学増刊号

      Volume: 26巻 Pages: 34-39

    • URL

      http://www.yodosha.co.jp/jikkenigaku/book/9784758103046/

    • Related Report
      2011 Final Research Report
  • [Journal Article] パーキンソン病の再生医療~ES細胞、iPS細胞を用いた細胞移植治療の展望~2009

    • Author(s)
      森実飛鳥、高橋淳
    • Journal Title

      綜合臨床 58

      Pages: 50-55

    • Related Report
      2009 Annual Research Report
  • [Journal Article] パーキンソン病に対する細胞移植治療~現在の到達点と今後の課題~2009

    • Author(s)
      森実飛鳥、高橋淳
    • Journal Title

      実験医学 増刊号 26

      Pages: 34-39

    • Related Report
      2009 Annual Research Report
  • [Presentation] カニクイザルパー一ンソン病モデルへのヒトES細胞由来ドーパミン神経細胞の移植2011

    • Author(s)
      森実飛鳥
    • Organizer
      第70回日本脳神経外科学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2011-10-12
    • Related Report
      2011 Final Research Report
  • [Presentation] カニクイザルパーキンソン病モデルへのヒトES細胞由来ドーパミン神経細胞の移植2011

    • Author(s)
      森実飛鳥、土井大輔、菊地哲広、吉川達也、尾上浩隆、林拓也、川崎俊之、高橋
    • Organizer
      第70回日本脳神経外科学会総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2011-10-12
    • Related Report
      2011 Annual Research Report
  • [Presentation] One-year observation of dopaminergic neurons derived from human embryonic stem cells in primate models of Parkinson's disease2011

    • Author(s)
      Morizane A
    • Organizer
      ISSCR(International Society for Stem Cell Research) 9th annual meeting
    • Place of Presentation
      Tronto, Canada
    • Year and Date
      2011-06-16
    • Related Report
      2011 Final Research Report
  • [Presentation] One-year observation of dopaminergic neurons derived from human embryonic stem cells in primate models of Parkinson's disease2011

    • Author(s)
      Morizane A, Doi D, Kikuchi T, Yoshikawa T, Unoe H, Hayashi T, Kawasaki T, Sasai Y, Suemori H, Takahashi J
    • Organizer
      ISSCR (International Society for Stem Cell Research) 9th annual meeting
    • Place of Presentation
      Tronto, Canada
    • Year and Date
      2011-06-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] Research for stem cell therapy with primate Parkinsonian model2011

    • Author(s)
      Morizane A
    • Organizer
      第6回研究所ネットワーク国際シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2011-06-09
    • Related Report
      2011 Final Research Report
  • [Presentation] Research for stem cell therapy with primate Parkinsonian model2011

    • Author(s)
      Morizane A, Takahashi J
    • Organizer
      第6回研究所ネットワーク国際シンポジウム
    • Place of Presentation
      東京医科歯科大学(東京)
    • Year and Date
      2011-06-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] ヒトES細胞を用いたカニクイザルパー一ンソン病モデルへの細胞移植2011

    • Author(s)
      森実飛鳥
    • Organizer
      第10回日本再生医療学会総会
    • Place of Presentation
      東京
    • Year and Date
      2011-03-01
    • Related Report
      2011 Final Research Report
  • [Presentation] ヒトES細胞を用いたカニクイザルパーキンソン病モデルへの細胞移植2011

    • Author(s)
      森実飛鳥
    • Organizer
      第10回日本再生医療学会総会
    • Place of Presentation
      東京
    • Year and Date
      2011-03-01
    • Related Report
      2010 Annual Research Report
  • [Presentation] Differences in neural differentiation propensity among cell lines of human pluripotent stem cells2010

    • Author(s)
      Morizane A
    • Organizer
      Neuroscience
    • Place of Presentation
      Diego, California
    • Year and Date
      2010-11-14
    • Related Report
      2011 Final Research Report
  • [Presentation] Differences in neural differrentiation propensity among cell lines of human pluripotent stem cells2010

    • Author(s)
      Asuka.Morizane
    • Organizer
      Neuroscience 2010 (Society for neuroscience)
    • Place of Presentation
      San Diego, California
    • Year and Date
      2010-10-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] Optimization of the protocol and cell line selection are important for generation of dopamine neurons from human induced pluripotentstem(iPS) cells2010

    • Author(s)
      Morizane A
    • Organizer
      Neuro Stemcell Workshop
    • Place of Presentation
      Mallorca, Spain
    • Year and Date
      2010-09-23
    • Related Report
      2011 Final Research Report
  • [Presentation] Optimization of the protocol and cell line selection are important for generation of dopamine neurons from human induced pluripotent stem(iPS)cells.2010

    • Author(s)
      Asuka Morizane
    • Organizer
      NeuroStemcell Workshop
    • Place of Presentation
      Mallorca, Spain
    • Year and Date
      2010-09-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] サルiPS細胞からのドーパミン神経分化誘導2010

    • Author(s)
      森実飛鳥
    • Organizer
      神経組織の成長・再生・移植研究会 第25回学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2010-05-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] 低分子化合物を用いたヒト多能性幹細胞からの神経誘導2010

    • Author(s)
      森実飛鳥
    • Organizer
      第9回日本再生医療学会総会
    • Place of Presentation
      広島
    • Year and Date
      2010-03-18
    • Related Report
      2011 Final Research Report
  • [Presentation] 低分子化合物を用いたヒト多能性幹細胞からの神経誘導2010

    • Author(s)
      森実飛鳥, 土井大輔, 菊地哲広, 高橋淳
    • Organizer
      第9回 日本再生医療学会総会
    • Place of Presentation
      広島
    • Year and Date
      2010-03-18
    • Related Report
      2009 Annual Research Report
  • [Presentation] Small molecule promote neural differentiation from human pluripotent stem cells in the stromal(PA6) cell co-culture condition2009

    • Author(s)
      Morizane A
    • Organizer
      Neuroscience
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2009-10-18
    • Related Report
      2011 Final Research Report
  • [Presentation] Small molecule promote neural differentiation from human pluripotent stem cells in the stromal (PA6) cell coculture condition.2009

    • Author(s)
      Asuka Morizane, D.Doi, T.Kikuc hi, J Takahashi
    • Organizer
      Neuroscience 2009
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2009-10-18
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヒト多能性幹細胞からの神経誘導におけるNodal/BMP抑制の役割2009

    • Author(s)
      森実飛鳥
    • Organizer
      第68回日本脳神経外科学会総会
    • Place of Presentation
      東京
    • Year and Date
      2009-10-14
    • Related Report
      2011 Final Research Report
  • [Presentation] ヒト多能性幹細胞からの神経誘導におけるNodal/BMP抑制の役割2009

    • Author(s)
      森実飛鳥、土井大輔、菊地哲広、宮本享、高橋淳
    • Organizer
      第68回 日本脳神経外科学会総会
    • Place of Presentation
      東京
    • Year and Date
      2009-10-14
    • Related Report
      2009 Annual Research Report
  • [Presentation] 基礎研究から臨床応用へ: ES細胞、ips細胞を用いたパー一ンソン病に対する細胞移植治療の将来展望2009

    • Author(s)
      森実飛鳥
    • Organizer
      第14回静岡健康
    • Place of Presentation
      静岡
    • Year and Date
      2009-10-02
    • Related Report
      2011 Final Research Report
  • [Presentation] 基礎研究から臨床応用へ : ES細胞、iPS細胞を用いたパーキンソン病に対する細胞移植治療の将来展望2009

    • Author(s)
      森実飛鳥
    • Organizer
      第14回静岡健康、長寿フォーラム
    • Place of Presentation
      静岡
    • Year and Date
      2009-10-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] Dopaminergic differentiation of human embryonic stem cells and iPS cells2009

    • Author(s)
      Morizane A
    • Organizer
      AXREGEN CoE and Neuro Fortis Workshop
    • Place of Presentation
      Lund, Sweden
    • Year and Date
      2009-09-18
    • Related Report
      2011 Final Research Report
  • [Presentation] Dopaminergic differentiation of human embryonic stem cells and iPS cells2009

    • Author(s)
      Asuka Morizane
    • Organizer
      AXREGEN, NCoE and NeuroFortis Workshop
    • Place of Presentation
      Lund, Sweden
    • Year and Date
      2009-09-18
    • Related Report
      2009 Annual Research Report
  • [Book] Perspectives of Stem Cells ?From Tools for Studying Mechanisms of Neuronal Differentiation towards Therapy-2010

    • Author(s)
      Henning Ulrich(Editor)
    • Publisher
      Springer
    • Related Report
      2011 Final Research Report
  • [Book] Perspectives of Stem Cells -From Tools for Studying Mechanisms of Neuronal Differentiation towards Therapy-2009

    • Author(s)
      Henning Ulrich (Editor)
    • Total Pages
      289
    • Publisher
      Springer
    • Related Report
      2009 Annual Research Report
  • [Remarks] ホームページ

    • URL

      http://www.frontier.kyoto-u.ac.jp/caO1/index.html

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.frontier.kyoto-u.ac.jp/ca01/index.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.frontier.kyoto-u.ac.jp/ca01/index.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.frontier.kyoto-u.ac.jp/ca01/index.html

    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] 多能性幹細胞の神経前駆細胞への分化誘導法2010

    • Inventor(s)
      高橋淳、森実飛鳥
    • Industrial Property Rights Holder
      京都大学
    • Filing Date
      2010-04-30
    • Related Report
      2011 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] Method for inducing differentiationof pluripotent stem cells into neural2010

    • Inventor(s)
      高橋淳、森実飛鳥
    • Industrial Property Rights Holder
      京都大学
    • Filing Date
      2010-08-12
    • Related Report
      2011 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] Method for inducing differentiation of pluripotent stem cells into neural precursor cells2010

    • Inventor(s)
      高橋淳、森実飛鳥
    • Industrial Property Rights Holder
      京都大学
    • Filing Date
      2010-08-12
    • Related Report
      2010 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] Method for inducing differentiation to nerve precursor cell2009

    • Inventor(s)
      Jun Takahashi/ Asuka Morizane
    • Industrial Property Rights Holder
      Kyoto Univ
    • Filing Date
      2009-08-12
    • Related Report
      2009 Annual Research Report
    • Overseas

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Published: 2009-04-01   Modified: 2016-04-21  

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