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Investigation for the attenuation of arrhythmia related to human iPS cell-based cardiac regenerative therapy

Research Project

Project/Area Number 15K10209
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Sakaguchi Hisashi  京都大学, 医学研究科, 客員研究員 (40743026)

Co-Investigator(Kenkyū-buntansha) 池田 義  京都大学, 医学研究科, 准教授 (40281092)
南方 謙二  京都大学, 医学研究科, 講師 (60539675)
杉山 篤  東邦大学, 医学部, 教授 (60242632)
Co-Investigator(Renkei-kenkyūsha) YAMASHITA JUN  京都大学, その他部局等, 教授 (50335288)
Research Collaborator MASUMOTO HIDETOSHI  京都大学, 大学院医学研究科, 特定助教 (70645754)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsiPS細胞 / 心筋梗塞 / 重症心不全 / 致死性不整脈 / ホルター心電図 / マイクロミニピッグ / 心筋疾患外科学 / 致死的不整脈 / プログラム電気刺激
Outline of Final Research Achievements

The Holter ECG after human iPS cell-derived cardiac tissue transplantation showed no occurrence of lethal arrhythmia whereas there was the occurrence of ventricular tachycardia in sham group pigs after induction of myocardial infarction. The variability of QT interval is known to be a marker of arrhythmia and was lower in cell sheet transplantation group compared to that in sham group. Here we showed the safety of human iPS cell-based cardiac regenerative therapy using pigs with similar heart rate with human. We also showed the occurrence of Torsade de Pointes which is known to be a lethal arrhythmia after administration of already known cardiotoxic drugs. Here we showed a basis of the occurrence of arrhythmia related to human iPS cell-based cardiac regenerative therapy.

Report

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

    (16 results)

All 2017 2016 2015 Other

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (10 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Modelling Torsade de Pointes arrhythmias in vitro in 3D human iPS cell-engineered heart tissue2017

    • Author(s)
      Kawatou M, Masumoto H, Fukushima H, Morinaga G, Sakata R, Ashihara T, Yamashita JK
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 1078-1078

    • DOI

      10.1038/s41467-017-01125-y

    • NAID

      120006355764

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The myocardial regenerative potential of three-dimensional engineered cardiac tissues composed of multiple human iPS cell-derived cardiovascular cell lineages.2016

    • Author(s)
      Masumoto H, Nakane T, Tinney JP, Yuan F, Ye F, Kowalski WJ, Minakata K, Sakata R, Yamashita JK, Keller BB.
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 29933-29933

    • DOI

      10.1038/srep29933

    • NAID

      120005829361

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Green Tea Polyphenol Prevents Diabetic Rats From Acute Kidney Injury After Cardiopulmonary Bypass.2016

    • Author(s)
      Funamoto M, Masumoto H, Takaori K, Taki T, Setozaki S, Yamazaki K, Minakata K, Ikeda T, Hyon SH, Sakata R.
    • Journal Title

      Ann Thorac Surg

      Volume: 101 Issue: 4 Pages: 1507-13

    • DOI

      10.1016/j.athoracsur.2015.09.080

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Efficient long-term survival of cell grafts after myocardial infarction with thick viable cardiac tissue entirely from pluripotent stem cells.2015

    • Author(s)
      Matsuo T, Masumoto H, Tajima S, Ikuno T, Katayama S, Minakata K, Ikeda T, Yamamizu K, Tabata Y, Sakata R, Yamashita JK.
    • Journal Title

      Scientific Reports

      Volume: 5:16842 Issue: 1 Pages: 1-14

    • DOI

      10.1038/srep16842

    • NAID

      120005753829

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Human iPS cell-engineered heart tissue to reproduce drug-induced torsade de pointes in vitro.2017

    • Author(s)
      Kawatou M, Masumoto H, Sakata R, Ashihara T, Yamashita J
    • Organizer
      第81回日本循環器学会学術集会
    • Place of Presentation
      金沢市
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] Human iPS cell-derived cardiac tissue to reproduce “Torsade de Pointes”arrhythmia in vitro.2017

    • Author(s)
      Kawatou M, Masumoto H, Fukushima H, Morinaga G, Sakata R, Ashihara T, Yamashita J.K
    • Organizer
      European Society of Cardiology Congress 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The therapeutic potential of human iPS cell-derived cardiac tissue onto a porcine myocardial infarction model.2017

    • Author(s)
      Hirao S, Masumoto H, Nishio H, Kawatou M, Li Z, Kanemtitsu H, Ueyama K,Yamazaki K,Ikeda T,Tabata Y, Yamashita J.K, Minatoya K.
    • Organizer
      American Heart Association 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In vitro Torsade de Pointes arrhythmia model with 3D human iPS cell-engineered heart tissue2017

    • Author(s)
      Kawatou M, Masumoto H, Fukushima H, Morinaga G, Ashihara T, Yamashita J.K.
    • Organizer
      American Heart Association 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Invited Oral session Bioengineered cardiac cell sheets.2016

    • Author(s)
      Masumoto H.
    • Organizer
      AHA American Heart Association
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] ヒトiPS細胞由来心筋細胞および血管構成細胞を含む三次元人工心筋組織による心筋再生についての検討2016

    • Author(s)
      升本 英利,中根 武一郎,南方 謙二,池田 義,坂田 隆造
    • Organizer
      .第69回日本胸部外科学会定期学術集会
    • Place of Presentation
      岡山市
    • Year and Date
      2016-09-28
    • Related Report
      2016 Research-status Report
  • [Presentation] Therapeutic potential of human iPS cell-derived engineered cardiac tissue including cardiomyocytes and multiple vascular lineages for myocardial infarction.2016

    • Author(s)
      Masumoto H, Nakane T, J P.Tinney, F Yuan, F Ye, W J.Kowalski, Minakata K, Sakata R, Yamashita J K, B B.Keller
    • Organizer
      International Society for Stem Cell Research(ISSCR)
    • Place of Presentation
      San Francisco,USA
    • Year and Date
      2016-06-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒトiPS細胞由来心臓構成細胞を含む三次元人工心筋組織移植による心筋再生についての検討2016

    • Author(s)
      升本 英利,中根 武一郎,Joseph Tinney,南方 謙二,坂田 隆造,山下 潤,Bradley Keller.
    • Organizer
      第37回日本炎症・再生医学会
    • Place of Presentation
      京都市
    • Year and Date
      2016-06-16
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒトiPS細胞由来心臓組織シート移植はブタ心筋梗塞モデルにおいて不整脈リスクを増大させることなく心機能を改善する2016

    • Author(s)
      青木隆之、升本英利、南方謙二、池田 義、坂田隆造
    • Organizer
      第15回日本心臓血管外科再生治療研究会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2016-03-15
    • Related Report
      2015 Research-status Report
  • [Presentation] Transplantation of Genomic Integration-free Human iPS Cell-derived Cardiac Tissue Sheets into Porcine Infarct Hearts Produced No Lethal Arrhythmia: A Preclinical Study for a Safer Human iPS Cell Therapy2015

    • Author(s)
      Takayuki Aoki, Hidetoshi Masumoto, Hiroshi Ohara, Yuji Nakamura, Hiroko Izumi-Nakaseko, Kentaro Ando, Toho Univ, Tokyo, Japan; Takeshi Ikuno, Masahide Kawatou, Masanosuke Ishigami, Kenji Minakata, Tadashi Ikeda
    • Organizer
      American Heart Association scientific sessions 2015
    • Place of Presentation
      Orlando, America
    • Year and Date
      2015-11-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Book] Annual Review循環器:心筋再生医療の進歩2016

    • Author(s)
      升本英利、坂田隆造
    • Total Pages
      7
    • Publisher
      中外医学社
    • Related Report
      2015 Research-status Report
  • [Remarks] 京都大学心臓血管外科

    • Related Report
      2015 Research-status Report

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

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