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Research on elimination of heterogenity of iPS cells that is believed to be causative in the tumor formation.

Research Project

Project/Area Number 23618003
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Regenerative medicine
Research InstitutionTohoku University

Principal Investigator

SATO Takeya  東北大学, 医学(系)研究科(研究院), 助教 (10312696)

Co-Investigator(Kenkyū-buntansha) YANAGISAWA Teruyuki  東北大学, 大学院医学系研究科, 教授 (90133941)
Co-Investigator(Renkei-kenkyūsha) SUKEGAWA Jun  東北大学, 大学院医学系研究科, 准教授 (30187687)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords細胞 / トランスレーショナルリサーチ / 再生医学 / 薬剤反応性 / 細胞・組織 / 発生・分化
Research Abstract

Induced pluripotent stem cells are known to possess ability to differentiate into various types of cells and to proliferate infinitely in vitro. Whereas, these characters of iPS cells often induce tumor formation and irritable immune reactions against the host cells following differentiate into immunocompetent cells. Thus, involvement of "suicide genes" is prerequisite to reserve safety of iPS cells in the application of regenerative medicine. Our novel suicide gene approach utilizes a gene for human thymidylate kinase (tmpk) in combination with a non-toxic prodrug, azido-thymidine (AZT) which is converted into toxic metabolites, AZT-triphosphate that leads to induce cell death. We chose the CR4 promoter for tmpk gene that expresses only undifferentiated iPS cells to ensure the safety of usage of differentiated iPS cells by removing residual undifferentiated cells in the differentiated cell cluster after AZT-administration. We have validated effectiveness of our approach in vitro.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (30 results)

All 2014 2013 2012 2011 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (22 results) Remarks (1 results)

  • [Journal Article] The Engineered Thymidylate Kinase (TMPK)/AZT Enzyme-Prodrug Axis Offers Efficient Bystander Cell Killing for Suicide Gene Therapy of Cancer.2013

    • Author(s)
      Sato T., Neschadim A., Lavie A., Yanagisawa T., Medin JA.
    • Journal Title

      PLOS one

      Volume: 8 Issue: 10 Pages: e78711-e78711

    • DOI

      10.1371/journal.pone.0078711

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interaction of PICK1 with C-Terminus of Growth Hormone–Releasing Hormone Receptor (GHRHR) Modulates Trafficking and Signal Transduction of Human GHRHR2013

    • Author(s)
      Katsushima Y, Sato T., Yamada C., Ito M., Suzuki Y., Ogawa E., Sukegawa I., Sukegawa J., Fukunaga K., Yanagisawa T.
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 122 Issue: 3 Pages: 193-204

    • DOI

      10.1254/jphs.12287FP

    • NAID

      10031185413

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of adenylyl cyclase-mediated cAMP production by plasma membrane associated cytoskeletal protein 4.1G2013

    • Author(s)
      Goto T, Chiba A, Sukegawa J, Yanagisawa T, Saito M, Nakahata N
    • Journal Title

      Cell Signal

      Volume: 25 Issue: 3 Pages: 690

    • DOI

      10.1016/j.cellsig.2012.11.020

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cell Fate Control Gene Therapy Based on Engineered Variants of Human Deoxycytidine Kinase2012

    • Author(s)
      Sato T
    • Journal Title

      Molecular Therapy

      Volume: 20 Issue: 5 Pages: 1002-1013

    • DOI

      10.1038/mt.2011.298

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] ミトコンドリア品質管理機構の分子薬理学的研究2012

    • Author(s)
      佐藤岳哉
    • Journal Title

      PCEM (Tohoku University)

      Volume: 31 Pages: 25-29

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The hydrophobic amino acids in putative helix 8 in carboxy-terminus of histamine H3 receptor are involved in receptor-G-protein coupling2011

    • Author(s)
      Kuramasu A, Yanai K, et al
    • Journal Title

      Cell Signal

      Volume: 23(11) Issue: 11 Pages: 1843-1849

    • DOI

      10.1016/j.cellsig.2011.06.021

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The hydrophobic amino acids in putative helix 8 in carboxy-terminus of histamine H3 receptor are involved in receptor-G-protein coupling.2011

    • Author(s)
      Kuramasu A., Sukegawa J., Sato T., Sakurai E., Watanabe T., Yanagisawa T., Yanai K.
    • Journal Title

      Cellular Signalling

      Volume: 23 Pages: 1843-1849

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 高活性化TMPKとAZTによる遺伝子治療法は、Bystander効果によりガンに対する治療効果を発揮する2014

    • Author(s)
      佐藤岳哉
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台市
    • Related Report
      2013 Final Research Report
  • [Presentation] カリウムチャネル開口薬の発見、開発、進歩2014

    • Author(s)
      柳澤輝行
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台市
    • Related Report
      2013 Final Research Report
  • [Presentation] 基礎医学研究・教育と薬理学会とを活性化する方略2014

    • Author(s)
      柳澤輝行
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台市
    • Related Report
      2013 Final Research Report
  • [Presentation] 高活性化TMPKとAZTによる遺伝子治療法は、Bystander効果によりガンに対する治療効果を発揮する2014

    • Author(s)
      佐藤岳哉
    • Organizer
      日本薬理学会 第87回年会
    • Place of Presentation
      仙台国際センター
    • Related Report
      2013 Annual Research Report
  • [Presentation] AZT活性化体細胞内蓄積はミトコンドリア呼吸能低下をもたらす2013

    • Author(s)
      佐藤岳哉、野村亮介、久志本成樹、柳澤輝行
    • Organizer
      第64回日本薬理学会北部会
    • Place of Presentation
      旭川市
    • Year and Date
      2013-09-13
    • Related Report
      2013 Final Research Report
  • [Presentation] AZT active metabolite impairs mitochondrial quality control system2013

    • Author(s)
      野村亮介、久志本成樹、柳澤輝行、佐藤岳哉
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡市
    • Related Report
      2013 Final Research Report
  • [Presentation] AZT活性化体細胞内蓄積はミトコンドリア呼吸能低下をもたらす2013

    • Author(s)
      佐藤岳哉 野村亮介、久志本成樹、柳澤輝行
    • Organizer
      日本薬理学会 第64回北部会
    • Place of Presentation
      旭川市大雪クリスタルホール
    • Related Report
      2013 Annual Research Report
  • [Presentation] AZT active metabolite imapirs mitochondrial quality control system2013

    • Author(s)
      佐藤 岳哉、野村 亮介、久志元 成樹、柳澤 輝行
    • Organizer
      第86回 日本薬理学会 年会
    • Place of Presentation
      福岡市
    • Related Report
      2012 Research-status Report
  • [Presentation] PICK1とGHRHRの相互作用による受容体作動活性の調節2012

    • Author(s)
      佐藤岳哉、伊東萌、助川淳、柳澤輝行
    • Organizer
      第63回日本薬理学会北部会
    • Place of Presentation
      新潟市
    • Year and Date
      2012-09-14
    • Related Report
      2013 Final Research Report
  • [Presentation] AZT誘発酸化ストレス応答遺伝子の発現解析2012

    • Author(s)
      野村亮介、久志本成樹、柳澤輝行、佐藤岳哉
    • Organizer
      第63回日本薬理学会北部会
    • Place of Presentation
      新潟市
    • Year and Date
      2012-09-14
    • Related Report
      2013 Final Research Report
  • [Presentation] ミトコンドリア品質管理機構の分子薬理学的研究2012

    • Author(s)
      佐藤岳哉
    • Organizer
      第63回東北臨床超微細形態懇話会
    • Place of Presentation
      仙台市
    • Year and Date
      2012-06-28
    • Related Report
      2013 Final Research Report
  • [Presentation] PICK1とGHRHRの相互作用はGHRHRの細胞表面発現を制御する2012

    • Author(s)
      佐藤岳哉、伊東萌、鈴木夕起、助川淳、柳澤輝行
    • Organizer
      第85回日本薬理学会年会
    • Place of Presentation
      京都市
    • Related Report
      2013 Final Research Report
  • [Presentation] AZT誘発ミトコンドリア機能不全の機能解析2012

    • Author(s)
      野村亮介、久志本成樹、柳澤輝行,佐藤岳哉
    • Organizer
      第85回日本薬理学会年会
    • Place of Presentation
      京都市
    • Related Report
      2013 Final Research Report
  • [Presentation] AZT誘発致死性ミオパチーは酸化ストレスにより誘発される2012

    • Author(s)
      柳澤輝行、野村亮介、助川淳、佐藤岳哉
    • Organizer
      第41回日本脈管作動物質学会年会
    • Place of Presentation
      秋田市
    • Related Report
      2013 Final Research Report
  • [Presentation] AZT誘発致死性ミオパチーは、酸化ストレスにより誘発される2012

    • Author(s)
      柳澤 輝行、野村 亮介、助川 淳、佐藤 岳哉
    • Organizer
      第41回 日本脈管作動物質学会 年会
    • Place of Presentation
      秋田市
    • Related Report
      2011 Research-status Report
  • [Presentation] PICK1とGHRHRの相互作用は、GHRHRの細胞表面発現を制御する2012

    • Author(s)
      佐藤岳哉、伊東萌、鈴木夕起、助川淳、柳澤輝行
    • Organizer
      第85回日本薬理学会年会
    • Place of Presentation
      京都市
    • Related Report
      2011 Research-status Report
  • [Presentation] AZT誘発ミトコンドリア機能不全の分子機構解析2012

    • Author(s)
      野村亮介、久志本成樹、柳澤輝行、佐藤岳哉
    • Organizer
      第85回日本薬理学会年会
    • Place of Presentation
      京都市
    • Related Report
      2011 Research-status Report
  • [Presentation] AZT誘発心筋ミトコンドリア機能障害は酸化ストレスによるものである2011

    • Author(s)
      佐藤岳哉、野村亮介、助川淳、柳澤輝行
    • Organizer
      第62回日本薬理学会北部会
    • Place of Presentation
      仙台市
    • Related Report
      2013 Final Research Report
  • [Presentation] AZT誘発心筋ミトコンドリア機能障害は、酸化ストレスによるものである2011

    • Author(s)
      佐藤 岳哉、野村 亮介、助川 淳、柳澤 輝行
    • Organizer
      第62回 日本薬理学会 北部会
    • Place of Presentation
      仙台市
    • Related Report
      2011 Research-status Report
  • [Presentation] ミトコンドリア品質管理機構の分子薬理学的研究

    • Author(s)
      佐藤 岳哉
    • Organizer
      第63回東北臨床超微形態懇話会
    • Place of Presentation
      仙台市
    • Related Report
      2012 Research-status Report
  • [Presentation] AZT誘発酸化ストレス応答遺伝子の発現解析

    • Author(s)
      野村 亮介、久志元 成樹、柳澤 輝行、佐藤 岳哉
    • Organizer
      第63回 日本薬理学会 北部会
    • Place of Presentation
      新潟市
    • Related Report
      2012 Research-status Report
  • [Presentation] PICK1とGHRHRの相互作用による受容体作動活性の調節

    • Author(s)
      佐藤 岳哉、伊東 萌、助川 淳、柳澤 輝行
    • Organizer
      第63回 日本薬理学会 北部会
    • Place of Presentation
      新潟市
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.med.tohoku.ac.jp/org/medical/11/index.html

    • Related Report
      2013 Final Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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