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Drug discovery for the treatment of severe heart failure

Research Project

Project/Area Number 25293297
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

Tsuneyosi Hiroshi  京都大学, 医学(系)研究科(研究院), その他 (40645412)

Co-Investigator(Kenkyū-buntansha) SAKATA RYUZO  京都大学, 大学院医学研究科, 名誉教授 (20325781)
丸井 晃  京都大学, 医学(系)研究科(研究院), 非常勤講師 (60402856)
升本 英利  京都大学, 医学(系)研究科(研究院), 助教 (70645754)
Co-Investigator(Renkei-kenkyūsha) YAMASHITA JUN  京都大学, ips細胞研究所, 教授 (50335288)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2013: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords心筋疾患外科学 / iPS細胞 / 創薬スクリーニング / 心筋症 / 重症心不全 / 創薬研究
Outline of Final Research Achievements

With regards to the establishment of cardiomyopathy patient’s iPS cells, we planned to collect the myocardial tissue intraoperatively in order to recognize the characteristics of pathology. And we carried out sampling in one case. With regards to iPS cell-derived cardiac tissue sheet, we differentiated cardiomyocytes and mural cells individually and made the sheets by mixing them in strict ratio. With regards to method of drug screening, we measured extracellular electrical potentials on the multi-electrode device. We focused on the assessment of cardio toxicity and used the E4031 that caused drug-induced QT prolongation. We reproduced QT (FPD: field potential duration) prolongation and characteristic re-entry type arrhythmia visually.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (32 results)

All 2016 2015 2014 2013 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (21 results) (of which Int'l Joint Research: 4 results) Book (2 results) Remarks (1 results)

  • [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 Annual Research 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 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Human iPS cell-engineered cardiac tissue sheets with cardiomyocytes and vascular cells for cardiac regeneration.2014

    • Author(s)
      Masumoto H, Ikuno T, Takeda M, Fukushima H, Marui A, Katayama S, Shimizu T, Ikeda T, Okano T, Sakata R, Yamashita JK.
    • Journal Title

      Sci Rep

      Volume: 4 Issue: 1 Pages: 6716-6716

    • DOI

      10.1038/srep06716

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of hepatocyte growth factor in myocarditis rats induced by immunization with porcine cardiac myosin.2014

    • Author(s)
      Nakano J, Ikeda T, Sakata R et al.
    • Journal Title

      Interact Cardiovasc Thorac Surg

      Volume: 18 Issue: 3 Pages: 300-307

    • DOI

      10.1093/icvts/ivt512

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of microRNA-145 to prevent vein graft disease in rabbits by regulation of smooth muscle cell phenotype.2014

    • Author(s)
      Ohnaka M, Ikeda T, Sakata R et al.
    • Journal Title

      J Thorac Cardiovasc Surg.

      Volume: 印刷中 Issue: 2 Pages: 676-682.e2

    • DOI

      10.1016/j.jtcvs.2013.11.054

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of chemicals inducing cardiomyocyte proliferation in developmental stage-specific manner with pluripotent stem cells2013

    • Author(s)
      Uosaki H, Magadum A, Seo K, Fukushima H, Takeuchi A, Nakagawa Y, Moyes KW, Narazaki G, Kuwahara K, Laflamme M, Matsuoka S, Nakatsuji N, Nakao K, Kwon C, Kass DA, Engel FB, Yamashita JK
    • Journal Title

      Circ Cardiovasc Genet

      Volume: 6(6) Issue: 6 Pages: 624-33

    • DOI

      10.1161/circgenetics.113.000330

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevention of retrosternal adhesion by novel biocompatible glue derived from food additives.2013

    • Author(s)
      Kamitani T, Ikeda T, Sakata R et al.
    • Journal Title

      J Thorac Cardiovasc Surg

      Volume: 146 Issue: 5 Pages: 1232-1238

    • DOI

      10.1016/j.jtcvs.2013.02.001

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Strategies in cell therapy for cardiac regeneration2013

    • Author(s)
      Masumoto H
    • Journal Title

      Inflammation and Regeneration

      Volume: 33 Issue: 2 Pages: 114-120

    • DOI

      10.2492/inflammregen.33.114

    • NAID

      130004943839

    • ISSN
      1880-8190, 1880-9693
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] ブタ心筋梗塞モデルを用いたiPS細胞由来心臓組織シート移植による不整脈評価実験2015

    • Author(s)
      幾野 毅、坂田隆造、山下潤 他
    • Organizer
      第37回日本バイオマテリアル学会大会
    • Place of Presentation
      京都市
    • Year and Date
      2015-11-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] Human iPS cell-derived 3D engineered cardiac tissue including cardiomyocytes and multiple vascular lineages for cardiac regeneration.2015

    • Author(s)
      Masumoto H, Sakata R, Yamashita JK et al.
    • Organizer
      American Heart Association 2015
    • Place of Presentation
      Orlando, USA
    • Year and Date
      2015-11-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [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 therapy.2015

    • Author(s)
      Aoki T, Sakata R, Yamashita JK et al.
    • Organizer
      American Heart Association 2015
    • Place of Presentation
      Orlando, USA
    • Year and Date
      2015-11-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ardiac tissue sheet including human iPS cell-derived cardiomyocytes and vascular cells restores impaired left ventricular systolic function of infarcted porcine hearts: a preclinical study.2015

    • Author(s)
      Masumoto H, Sakata R, Yamashita JK et al.
    • Organizer
      European Society of Cardiology (ESC) Congress
    • Place of Presentation
      London, UK
    • Year and Date
      2015-08-29
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of 3D Engineered Cardiac Tissue with Human iPS Cell-derived Cardiomyocytes and Endothelial Cells.2015

    • Author(s)
      Masumoto H, Sakata R, Yamashita JK et al.
    • Organizer
      Annual Meeting of International Society of Stem Cell Research (ISSCR).
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      2015-06-24
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 多能性幹細胞による心筋再生研究の最前線2015

    • Author(s)
      升本 英利
    • Organizer
      第45回日本心臓血管外科学会学術総会
    • Place of Presentation
      京都
    • Year and Date
      2015-02-16 – 2015-02-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] ミニブタ心筋梗塞モデルへのヒト iPS 細胞由来心臓組織シート移植は心機能を回復する2015

    • Author(s)
      石上雅之助
    • Organizer
      第45回日本心臓血管外科学会学術総会
    • Place of Presentation
      京都
    • Year and Date
      2015-02-16 – 2015-02-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 2 型 VEGF 受容体陽性細胞純化再培養によるヒト iPS 細胞からの効率的血管内 皮細胞分化誘導2015

    • Author(s)
      幾野 毅
    • Organizer
      第45回日本心臓血管外科学会学術総会
    • Place of Presentation
      京都
    • Year and Date
      2015-02-16 – 2015-02-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Transplantation of cardiac cell sheet including human iPS cell-derived cardiomyocytes and vascular cells to infarcted porcine heart restores impaired left ventricular global function and dyssynchrony2014

    • Author(s)
      Ishigami M
    • Organizer
      AHA2014
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] ミニブタ心筋梗塞モデルへのヒトiPS 細胞由来心臓組織シート移植による心機能回復2014

    • Author(s)
      石上 雅之助
    • Organizer
      第67回日本胸部外科学会定期学術集会
    • Place of Presentation
      福岡市
    • Year and Date
      2014-09-30 – 2014-10-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] 2型血管内皮細胞増殖因子受容体陽性細胞の純化再培養によるヒトiPS 細胞からの血管内皮細胞分化誘導の効率化2014

    • Author(s)
      幾野 毅
    • Organizer
      第67回日本胸部外科学会定期学術集会
    • Place of Presentation
      福岡市
    • Year and Date
      2014-09-30 – 2014-10-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Scalable and highly efficient endothelial cell differentiation methods from human induced pluripotent stem cells based on monolayer and serum-free culture2014

    • Author(s)
      Ikuno T
    • Organizer
      ESC Congress 2014
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2014-08-30 – 2014-09-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Scalable and highly efficient endothelial cell differentiation methods from human induced pluripotent stem cells based on monolayer and serum-free culture for realization of regenerative medicine2014

    • Author(s)
      Ikuno T
    • Organizer
      International Society for Stem Cell Research (ISSCR)
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2014-06-18 – 2014-06-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] High-purity and scalable endothelial cell differentiation methods from human induced pluripotent stem cells based on monolayer and serum-free culture2014

    • Author(s)
      Ikuno T
    • Organizer
      18th International Vascular Biology Meeting
    • Place of Presentation
      Kyoto
    • Year and Date
      2014-04-14 – 2014-04-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] CELL SHEET TRANSPLANTATION TO RAT INFARCT HEART USING GENOMIC INTEGRATION-FREE HUMAN IPS CELLS GENERATED WITH EPISOMAL PLASMID VECTORS: A STRATEGY FOR TUMOR-FREE CARDIAC CELL THERAPY2014

    • Author(s)
      Masumoto H., Marui A., Sakata R., Yamashita JK. et al.
    • Organizer
      ISSCR(International Society for Stem Cell Research) 12th Annual Meeting
    • Place of Presentation
      Vancouver, Canada
    • Related Report
      2013 Annual Research Report
  • [Presentation] 多能性幹細胞由来心臓組織様シートの効果的積層化は移植細胞の生着効率を改善し心筋梗塞後の心機能低下を抑制する2013

    • Author(s)
      松尾 武彦, 升本 英利, 丸井 晃, 坂田 隆造ほか
    • Organizer
      第66回日本胸部外科学会定期学術集会
    • Place of Presentation
      仙台市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 再生医学研究が変える外科の近未来 細胞シート技術を用いた多能性幹細胞による心筋再生研究 機能的再生から組織再生へ2013

    • Author(s)
      升本 英利, 丸井 晃, 山下 潤, 坂田 隆造ほか
    • Organizer
      第113回日本外科学会定期学術集会
    • Place of Presentation
      福岡市
    • Related Report
      2013 Annual Research Report
  • [Presentation] The Transplantation of Human iPS Cell-Derived Cardiac Cell Sheets to Rat Myocardial Infarction Model Ameliorates Cardiac Dysfunction Through Neovascularization.2013

    • Author(s)
      Masumoto H., Marui A., Sakata R., Yamashita JK et al.
    • Organizer
      The 21st Annual Meeting Of The Asian Society For Cardiovascular And Thoracic Surgery (ASCVTS2013)
    • Place of Presentation
      神戸市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Transplantation of Human Induced Pluripotent Stem Cell-Engineered Tissue Sheets with Defined Cardiovascular Cell Populations for Infarcted Rat Hearts2013

    • Author(s)
      Masumoto H., Marui A., Sakata R., Yamashita JK. et al.
    • Organizer
      ISSCR(International Society for Stem Cell Research) 11th Annual Meeting
    • Place of Presentation
      Boston, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] An efficient piling up of pluripotent stem cell-derived cardiac tissue-like sheets that robustly promotes cell engraftment and ameliorates cardiac dysfunction after myocardial infarction2013

    • Author(s)
      Matsuo T., Masumoto H., Marui A., Sakata R., Yamashita JK.et al.
    • Organizer
      ESC (European Society for Cardiology) Congress2013
    • Place of Presentation
      Amsterdam, Netherlands
    • Related Report
      2013 Annual Research Report
  • [Presentation] Safety and Efficacy of Sustained Release of basic fibroblast growth factor Using Biodegradable Gelatin Hydrogel in Patients With Critical Limb Ischemia2013

    • Author(s)
      Matsuo T., Masumoto H., Marui A., Sakata R., Yamashita JK.et al.
    • Organizer
      AHA (American Heart Association) Scientific Sessions 2013
    • Place of Presentation
      Dallas, USA
    • Related Report
      2013 Annual Research Report
  • [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 Annual Research Report
  • [Book] Pluripotent Stem Cells, ISBN 978-953-51-1192-42013

    • Author(s)
      Masumoto H, Yamashita JK
    • Total Pages
      372
    • Publisher
      InTech
    • Related Report
      2013 Annual Research Report
  • [Remarks] 京都大学 心臓血管外科

    • URL

      http://kyoto-cvs.jp/

    • Related Report
      2013 Annual Research Report

URL: 

Published: 2013-05-21   Modified: 2019-07-29  

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