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Identification of the mechanisms for hereditary arrhythmic disease using human iPS cell technology

Research Project

Project/Area Number 25461117
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionKeio University

Principal Investigator

Murata Mitsushige  慶應義塾大学, 医学部, 講師 (30317135)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywords心臓 / 再生医療 / 不整脈 / イオンチャネル / iPS細胞 / 心筋細胞
Outline of Final Research Achievements

We have previously reported that human induced pluripotent stem (iPS) cell technology is useful for disease specific in vivo cell model and drug screening. Since many kinds of ion channels express in the cardiomyocytes, it is desirable to investigate the effects of anti-arrhythmic drugs on electrophysiological properties in native cardiomyocytes.
In this study, first, we have succeeded in the induction of human iPS cell derived cardiomyocytes. QT PCR analyses revealed the expression of several ion channels such as SCN5A、CACNA1G、HCN4 in undifferentiated human iPS cells. Second, we investigated the effects of Bepridil on ion channel expression in human iPS cell derived cardiomyocytes. Bepridil dose dependently increased the expression of SCN5A, CACNA1, CACNA1G, HCN4. These results indicated that Bepridil may modulate ion channel expression in cardiomyocytes, resulting in the chronic effects of Bepridil in addition to the acute direct effect on the ion channels.

Report

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

    (14 results)

All 2015 2014 2013

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Significance of Echocardiographic Assessment for Right Ventricular Function after Balloon Pulmonary Angioplasty in Patients with Chronic Thromboembolic Induced Pulmonary Hypertension2015

    • Author(s)
      Tsugu T, Murata M, Kawakami T, Yasuda R, Tokuda H, Minakata Y, Tamura Y, Kataoka M, Hayashida K, Tsuruta H, Maekawa Y, Inoue S, Fukuda K
    • Journal Title

      Am J Cardiol

      Volume: 115 Issue: 2 Pages: 256-261

    • DOI

      10.1016/j.amjcard.2014.10.034

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation and characterization of functional cardiomyocytes derived from human T cell-derived induced pluripotent stem cells.2014

    • Author(s)
      Seki T, Yuasa S, Kusumoto D. Tohyama S, et al.
    • Journal Title

      PLoS One.

      Volume: 9 Issue: 1 Pages: 1-7

    • DOI

      10.1371/journal.pone.0085645

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suppression of Rad leads to arrhythmogenesis via PKA-mediated upregulation of Ryanodine receptor activity in the heart.2014

    • Author(s)
      Yamakawa H, Murata M, Suzuki T, Yada H, Ishida H, Aizawa Y, Adachi T, Kamiya K, Fukuda K.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 452 Issue: 3 Pages: 701-707

    • DOI

      10.1016/j.bbrc.2014.08.126

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Distinct Metabolic Flow Enable Large-Scale Purification of Mouse and Human Pluripotent Stem Cell-Derived Cardiomyocytes.2013

    • Author(s)
      Tohyama S, Hattori F, Sano M, et al.
    • Journal Title

      Cell Stem Cell

      Volume: 12 Issue: 1 Pages: 127-37

    • DOI

      10.1016/j.stem.2012.09.013

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Brugada syndrome behind complete right bundle-branch blosk2013

    • Author(s)
      Aizawa Y, Takatsuki S, Sano M, Kimura T, Nishiyama N, Fukumoto K, Tanimoto Y, Tanimoto K, Murata M, Komatsu T, Mitamura H, Ogawa S, Funazaki T, Sato M, Aizawa Y, Fukuda K
    • Journal Title

      Circulation

      Volume: 128 Issue: 10 Pages: 1048-1054

    • DOI

      10.1161/circulationaha.113.003472

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diagnostic value of portable electrocardiogram (Cardiophone) in patients complaining of palpitation2013

    • Author(s)
      Aizawa Y, Takatsuki S, Suenaga Y, Kimura T, Nishiyama N, Fukumoto K, Tanimoto Y, Tanimoto K, Kohsaka S, Fukuda Y, Murata M, Miyoshi S, Sato T, Iwanaga S, Ogawa S, Fukuda K
    • Journal Title

      International Journal of Cardiolgy

      Volume: 168 Issue: 3 Pages: 2925-2927

    • DOI

      10.1016/j.ijcard.2013.03.182

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Distinct iPS Cells shows different Cardiac Differentiation Efficiency.2013

    • Author(s)
      Ohno Y, Yuasa S, Seki T, Fukuda K., et al.
    • Journal Title

      Stem Cells International

      Volume: 2013 Pages: 659739-659739

    • DOI

      10.1155/2013/659739

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Echocardiographic evaluation of the mechanisms for right ventricular dysfunction in chronic thromboembolic pulmonary hypertension2015

    • Author(s)
      39.Tsugu T, Murata M, Kawakami T, Tokuda H, Minakata Y, Kataoka M, Tsuruta H, Itabashi Y, Kanazawa H, Mahara K, Fukuda K
    • Organizer
      88th American Heart Association scientific meeting
    • Place of Presentation
      Orland, USA
    • Year and Date
      2015-11-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RV dyssynchrony predicts clinical outcomes after balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension2015

    • Author(s)
      38.Tsugu T, Murata M, Kawakami T, Tokuda H, Minakata Y, Kataoka M, Tsuruta H, Itabashi Y, Kanazawa H, Fukuda K
    • Organizer
      European Society of Cardiology annual meeting
    • Place of Presentation
      London, UK
    • Year and Date
      2015-08-29
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pathophysiological analysis of the hereditary heart disease using iPS cells2015

    • Author(s)
      153.Kuroda Y, Yuasa S, Watanabe Y, Hattori T, Ohno S, Egashira T, Seki T, Okata S, Tanaka A, Aizawa Y, Suzuki T, Murata M, Aiba T, Makita N, Shimizu W, Kodama I, Horie M, Horigome H, Kamiya K, Fukuda K.
    • Organizer
      第79回日本循環器学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2015-04-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] Uncovering the Pathophysiology of Short-coupled Variant of Torsade de Pointes by Disease Specific-induced Pluripotent Stem Cells2014

    • Author(s)
      Suzuki T, Yuasa S, Takei M, Murata M, Kamiya K, Fukuda K
    • Organizer
      第78回日本循環器学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Disease Modeling for Andersen-Tawil Syndrome Using Patient-Specific iPS Cell2014

    • Author(s)
      Kuroda Y, Yuasa S, Hattori T, egashira T, Aizawa Y, Seki T, Murata M, Okata S, Ohno S, Horie M, Fukuda K, Kamiya K
    • Organizer
      第78回日本循環器学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Disease Modeling Using iPS Cells2014

    • Author(s)
      Furukawa T, Okata S, Yuasa S, Suzuki T, Makita N, Kurokawa J, Egashira T, Yamakawa H, Seki T, Aizawa T, Hashimoto H, Kudoda Y, Tanaka A, Yae K, Murata M, Aiba T, Shimizu W, Horie M, Kodama I, Ogawa S, Fukuda K
    • Organizer
      第78回日本循環器学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Clinical applications of tissue imaging for specific cases2013

    • Author(s)
      Murata M
    • Organizer
      2013 American Society of Echocardiography Annual Scientific Meeting
    • Place of Presentation
      Minneapolis
    • Related Report
      2013 Research-status Report
    • Invited

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Published: 2014-07-25   Modified: 2019-07-29  

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