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2013 Fiscal Year Final Research Report

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

Research Project

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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
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
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.

  • Research Products

    (19 results)

All 2014 2013 2012 2011 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (12 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 Cancer2013

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

      PLOS ONE

      Volume: 8 Pages: e78711

    • DOI

      10.1371/journal.pone.0078711

    • 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

      J. Pharmacol. Sci.

      Volume: 122 Pages: 193-204

    • DOI

      10.1254/jphs.12287FP

    • 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 Pages: 690-697

    • DOI

      10.1016/j.cellsig.2012.11.020

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

    • Author(s)
      Neschadim A., Wang JCM., Sato T., Fowler DH., Lavie A., Medin JA.
    • Journal Title

      Mol Ther

      Volume: 20(5) Pages: 1002-1013

    • DOI

      10.1038/mt.2011.298

    • 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

    • 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., Sukegawa J., Sato T., Sakurai E., Watanabe T., Yanagisawa T., Yanai K
    • Journal Title

      Cell Signal

      Volume: 23 Pages: 1843–1849

    • DOI

      10.1016/j.cellsig.2011.06.021

    • 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
    • Year and Date
      20140319-21
  • [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
    • Year and Date
      20140319-21
  • [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
    • Year and Date
      20140319-21
  • [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
    • Year and Date
      20130321-23
  • [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
  • [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
    • Year and Date
      20120314-16
  • [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
    • Year and Date
      20120314-16
  • [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
    • Year and Date
      20120210-11
  • [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
  • [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
  • [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
  • [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
    • Year and Date
      20110929-30
  • [Remarks]

    • URL

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

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Published: 2015-07-16  

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