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Eliminating residual undifferentiated cells from iPSC-CMs for safer clinical application of iPSCs

Research Project

Project/Area Number 15K10211
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular surgery
Research InstitutionOsaka University

Principal Investigator

Masuda Shigeo  大阪大学, 医学系研究科, 特任准教授(常勤) (10396749)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsヒトiPS細胞 / 造腫瘍性 / 未分化細胞除去 / 分子標的治療薬
Outline of Final Research Achievements

Clinical application of iPS-derived cardiomyocytes (iPS-CMs) is considered to be one of the most promising approach to regenerative treatment for severe heart failure. However, its success would largely depend on safety, including prevention of tumor formation (Masuda S, et al. Nature Rev Cardiol. 2014;11:553-4). Here, we demonstrate that BET protein bromodomain antagonist is efficacious in removing residual undifferentiated cells in vitro. In this context, it was revealed that BET protein antagonist functions as a Nanog inhibitor within human iPS cells. Furthermore, co-treatment with BET protein antagonist and CDK inhibitors (CDK9 or CDK1 inhibitor) synergistically eliminated residual undifferentiated cells among human iPS-CMs. These findings imply that combination treatment in vitro with these drugs contributes to molecular-targeted treatment on “human iPS cells”.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (26 results)

All 2018 2017 2016 2015

All Journal Article (10 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 8 results,  Open Access: 2 results) Presentation (11 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Book (5 results)

  • [Journal Article] Pivotal role of non-cardiomyocytes in electromechanical and therapeutic potential of induced pluripotent stem cell-derived engineered cardiac tissue.2018

    • Author(s)
      Iseoka H, Miyagawa S, Fukushima S, Saito A, Masuda S, Yajima S, Ito E, Sougawa N, Takeda M, Harada A, Lee JK, Sawa Y.
    • Journal Title

      Tissue Eng Part A.

      Volume: 24(3-4) Issue: 3-4 Pages: 287-300

    • DOI

      10.1089/ten.tea.2016.0535

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Atherosclerosis: Caused by Mutated Old Blood Cells.2017

    • Author(s)
      Masuda S.
    • Journal Title

      Ann Cardiol Cardiovasc Med.

      Volume: 1(1) Pages: 1002-1002

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Highly Durable RNAi Therapeutic Inhibitor of PCSK9.2017

    • Author(s)
      Masuda S, Miyagawa S, Sawa Y.
    • Journal Title

      N Engl J Med.

      Volume: 376(18) Issue: 18 Pages: e38-e38

    • DOI

      10.1056/nejmc1703361

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Correspondence: A Highly Durable RNAi Therapeutic Inhibitor of PCSK9.2017

    • Author(s)
      Masuda S, Miyagawa S, Sawa Y.
    • Journal Title

      N Engl J Med.

      Volume: 印刷中

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Expandable progenitors from induced pluripotent stem cells.2016

    • Author(s)
      Masuda S, Miyagawa S, Fukushima S, Nakamura T, Khurram MA, Ishikawa T, Saito A, Sawa Y.
    • Journal Title

      Nature Rev Cardiol.

      Volume: 13(10) Issue: 10 Pages: 574-574

    • DOI

      10.1038/nrcardio.2016.129

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Brentuximab vedotin for CD30-positive tumours.2016

    • Author(s)
      Masuda S, Miyagawa S, Nakamura T, Khurram MA, Sawa Y.
    • Journal Title

      Lancet Oncol.

      Volume: 17(9) Issue: 9 Pages: e371-e371

    • DOI

      10.1016/s1470-2045(16)30404-1

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Teratocarcinomas Arising from Allogeneic Induced Pluripotent Stem Cell-Derived Cardiac Tissue Constructs Provoked Host Immune Rejection in Mice.2016

    • Author(s)
      Kawamura A, Miyagawa S, Fukushima S, Kawamura T, Kashiyama N, Ito E, Watabe T, Masuda S, Toda K, Hatazawa J, Morii E, Sawa Y.
    • Journal Title

      Scientific Reports

      Volume: 29 Issue: 1 Pages: 22130-22130

    • DOI

      10.1038/srep19464

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Building a new treatment for heart failure-Transplantation of Induced Pluripotent Stem Cell-derived Cells into the Heart.2016

    • Author(s)
      Miyagawa S, Fukushima S, Imanishi Y, Kawamura T, Mochizuki-Oda N, Masuda S, Sawa Y.
    • Journal Title

      Curr Gene Ther.

      Volume: 16(1) Pages: 5-13

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] CD30-targeting immunoconjugates and bystander effects.2015

    • Author(s)
      Masuda S, Miyagawa S, Sougawa N, Sawa Y.
    • Journal Title

      Nat Rev Clin Oncol.

      Volume: 12(4) Issue: 4 Pages: 245-245

    • DOI

      10.1038/nrclinonc.2014.159-c1

    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Journal Article] Eliminating residual iPS cells for safety in clinical application.2015

    • Author(s)
      Masuda S, Miyagawa S, Fukushima S, Sougawa N, Okimoto K, Tada C, Saito A, Sawa Y.
    • Journal Title

      Protein Cell.

      Volume: 6(7) Issue: 7 Pages: 469-471

    • DOI

      10.1007/s13238-015-0170-4

    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Novel PROTAC-induced BET Protein Degradation is Potent in Ex Vivo Purging of Tumorigenic Cells from iPSC-derived Cardiomyocytes.2018

    • Author(s)
      Masuda S, Miyagawa S, Kawaguchi K, Nishitani M, Ishikawa T, Saito A, Sawa Y.
    • Organizer
      第82回 日本循環器学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Novel Factors that Evaluate Safety in iPSC-derived Cardiomyocytes Contaminated with Tumorigenic Cells.2018

    • Author(s)
      Masuda S, Miyagawa S, Nishitani M, Kawaguchi K, Ishikawa T, Saito A, Sawa Y.
    • Organizer
      第82回 日本循環器学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Eliminating Residual Undifferentiated Cells from iPSC-derived Cardiomyocytes by Heat Shock Protein 90 Inhibitors in Collaboration with Proteasome Inhibitor.2018

    • Author(s)
      Masuda S, Miyagawa S, Nishitani M, Kawaguchi K, Ishikawa T, Saito A, Sawa Y.
    • Organizer
      第82回 日本循環器学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] BET Protein Antagonist is Potent in Eliminating Residual Undifferentiated Cells from Human iPS-derived Cardiomyocytes in Synergy with CDK Inhibitors2017

    • Author(s)
      Shigeo Masuda, Shigeru Miyagawa, Satsuki Fukushima, Terumi Nakamura, Kohei Kawaguchi, Tsuyoshi Ishikawa, Atsuhiro Saito, Yoshiki Sawa
    • Organizer
      第80回 日本循環器学会学術総会
    • Place of Presentation
      金沢
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] Heat shock protein 90 (HSP90)阻害剤を用いたヒトiPS由来未分化細胞除去の可能性2017

    • Author(s)
      増田 茂夫、宮川 繁、Maaz Asher Khurram、福嶌 五月、中村 照美、川口 耕平、石川 烈、齋藤 充弘、澤 芳樹
    • Organizer
      第16回 日本再生医療学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
  • [Presentation] Eliminating Residual Undifferentiated Cells from Human iPS-derived Products by Heat Shock Protein 90 Inhibitors.2017

    • Author(s)
      Masuda S, Miyagawa S, Khurram MA, Kawaguchi K, Ishikawa T, Saito A, Sawa Y.
    • Organizer
      15th International Society for Stem Cell Research: Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Novel Candidate Markers for Evaluating Safety in iPSC-derived Cardiomyocytes Contaminated with Tumorigenic Cells.2017

    • Author(s)
      Masuda S, Miyagawa S, Nakamura T, Nishitani M, Kawaguchi K, Ishikawa T, Saito A, Sawa Y.
    • Organizer
      American Heart Association Scientific Sessions 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] BET Protein Antagonist is Potent in Eliminating Residual Undifferentiated Cells from Human iPS-derived Cardiomyocytes in Synergy with CDK Inhibitors2016

    • Author(s)
      Shigeo Masuda, Shigeru Miyagawa, Satsuki Fukushima, Kaori Okimoto, Chika Tada, Yumi Ueda, Kohei Kawaguchi, Atsuhiro Saito, Yoshiki Sawa
    • Organizer
      14th International Society for Stem Cell Research: Annual Meeting
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2016-06-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 教育セッション(5) 幹細胞を用いた心不全科学 「iPS細胞の腫瘍原性」2015

    • Author(s)
      増田 茂夫、宮川 繁、福嶌 五月、澤 芳樹
    • Organizer
      第19回 日本心不全学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2015-10-22
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] DRUG RE-POSITIONING ENABLES ELIMINATION OF UNDIFFERENTIATED CELLS IN CLINICAL APPLICATION OF IPS CELLS.2015

    • Author(s)
      Masuda S, Miyagawa S, Fukushima S, Okimoto K, Ueda Y, Kawaguchi K, Mori D, Kawamura A, Ito E, Sougawa N, Imanishi Y, Saito A, Sawa Y.
    • Organizer
      13th International Society for Stem Cell Research: Annual Meeting
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      2015-06-24
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Drug Re-positioning Enables Elimination of Undifferentiated Cells in Clinical Application of iPS Cells.2015

    • Author(s)
      Masuda S, Miyagawa S, Fukushima S, Ueda Y, Kawaguchi K , Saito A, Sawa Y.
    • Organizer
      第79回 日本循環器学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2015-04-24
    • Related Report
      2015 Research-status Report
  • [Book] 腫瘍内科 「Notchシグナル阻害剤」2018

    • Author(s)
      増田茂夫
    • Total Pages
      7
    • Publisher
      科学評論社
    • Related Report
      2017 Annual Research Report
  • [Book] 日本再生医療学会雑誌2017

    • Author(s)
      増田茂夫、宮川繁、澤芳樹
    • Total Pages
      1
    • Publisher
      メディカルレビュー社
    • ISBN
      9784779219993
    • Related Report
      2017 Annual Research Report
  • [Book] Ex vivo Purging of Residual iPS Cells for Safer Clinical Application. (Chapter 6) (pp.117-126) In: Advances in Medicine and Biology (Volume 108), Leon V. Berhardt, ed.2016

    • Author(s)
      Masuda S
    • Total Pages
      10
    • Publisher
      Nova Publishers
    • Related Report
      2016 Research-status Report
  • [Book] がん分子標的治療 「Notchシグナル関連腫瘍に対する分子標的治療の進捗」2016

    • Author(s)
      増田茂夫
    • Total Pages
      5
    • Publisher
      メディカルレビュー社
    • Related Report
      2016 Research-status Report
  • [Book] 医学のあゆみ 「Chemical iPS細胞の展望」2015

    • Author(s)
      増田茂夫、澤芳樹
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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