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Pathophysiological analysis of Brugada syndrome using iPS cell-derived right ventricular cardiomyocytes

Research Project

Project/Area Number 21K16057
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53020:Cardiology-related
Research InstitutionOkayama University

Principal Investigator

Saito Yukihiro  岡山大学, 大学病院, 助教 (20724454)

Project Period (FY) 2021-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2021: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
KeywordsiPS細胞 / 右室心筋細胞 / 二次心臓領域 / Brugada症候群 / 右室
Outline of Research at the Start

Brugada症候群や不整脈源性右室心筋症は右室優位に病変を認め、植込み型除細動器以外の治療法は確立されていない。iPS細胞を用いた疾患モデル作製のため、右室心筋を誘導する必要があるが、その分化方法は確立されていない。そこで、iPS細胞から右室心筋細胞の誘導条件を確立する。また、Brugada症候群患者の細胞から作製したiPS細胞由来右室心筋を用いて、病態解析を行う。

Outline of Final Research Achievements

We established a method to induce left ventricular and right ventricular cardiomyocytes separately from healthy human iPS cells and found that the properties of left and right ventricular cardiomyocytes were different. The paper is currently being submitted for publication. In addition, we generated iPS cells from skin fibroblasts derived from three patients with Brugada syndrome, and induced differentiation of left ventricular and right ventricular cardiomyocytes from the iPS cell lines. Although it took time to optimize the combination of cell seeding density and concentration of low molecular weight compounds for each cell line, we were able to induce cardiomyocytes corresponding to left ventricular and right ventricular cardiomyocytes from all cell lines. Since we were not able to perform specific analysis, we plan to analyze the cardiomyocytes in the future.

Academic Significance and Societal Importance of the Research Achievements

ヒトiPS細胞によって、患者自身の心筋細胞を研究に用いることができるようになった。一方で、疾患を生じる心臓の部位には特徴のある疾患については、特徴を示しうる心筋細胞をiPS細胞から誘導することが重要であるはずである。本研究において確立された、健常人および患者由来iPS細胞から左室および右室心筋細胞を別々に効率よく誘導する方法は、Brugada症候群、不整脈原性右室心筋症、肺高血圧症、先天性心疾患などの右室疾患に対する細胞モデル研究をサポートする意義のある成果である。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (5 results)

All 2022 2021 Other

All Int'l Joint Research (1 results) Presentation (4 results) (of which Invited: 2 results)

  • [Int'l Joint Research] University of Wisconsin Madison(米国)

    • Related Report
      2022 Annual Research Report
  • [Presentation] Different Heart Field Progenitors and Chamber Cardiomyocytes Derived from Pluripotent Stem Cells2022

    • Author(s)
      斎藤幸弘、中村一文、伊藤浩
    • Organizer
      第86回日本循環器学会学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Characteristics of right ventricular cardiomyocytes derived from human pluripotent stem cells2022

    • Author(s)
      斎藤幸弘、中村一文、伊藤浩
    • Organizer
      第39回国際心臓研究学会日本部会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Different Heart Field Progenitors and Chamber Cardiomyocytes Derived from Pluripotent Stem Cells2022

    • Author(s)
      斎藤 幸弘、中村 一文、伊藤 浩
    • Organizer
      第86回日本循環器学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] ヒトiPS細胞由来右室心筋細胞の誘導2021

    • Author(s)
      斎藤 幸弘、中村 一文、伊藤 浩
    • Organizer
      第25回日本心不全学会学術集会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2024-01-30  

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