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Elucidation of the mechanism of arrhythmia in myocardial infarction in an organ-on-a-chip

Research Project

Project/Area Number 17KK0168
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research)

Allocation TypeMulti-year Fund
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionOkayama University

Principal Investigator

Takahashi Ken  岡山大学, 医歯薬学総合研究科, 研究准教授 (50432258)

Project Period (FY) 2018 – 2020
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥14,430,000 (Direct Cost: ¥11,100,000、Indirect Cost: ¥3,330,000)
Keywords臓器チップ / 心筋梗塞 / 脳梗塞 / TRPM4 / iPS細胞 / CRISPR/Cas9 / 虚血再灌流障害 / 腎臓移植 / 補体活性化 / 腎移植 / 虚血再灌流 / iPS
Outline of Final Research Achievements

The original one-year schedule was extended by four months, and research on ischemia-reperfusion injury was conducted using the organ-on-a-chip in the laboratory of Professor Donald E. Ingber of the Wyss Institute at Harvard University. I acquired techniques for organ-on-a-chip research and formed an international research network.
After returning to Japan, my research team succeeded in developing a human heart-on-a-chip using human iPS-derived cardiomyocytes under co-culture with human fibroblasts and human vascular endothelial cells.
Furthermore, we succeeded in knocking out TRPM4 channels in human iPS cells by genome editing using CRISPR/Cas9. This paved the way for investigating the involvement of this channel in the development of myocardial infarction.

Academic Significance and Societal Importance of the Research Achievements

臓器チップ技術を利用したヒト臓器モデルの開発と、それを利用した疾患モデルの開発に大きな成果が得られた。その結果、これまで実験動物に頼らざるを得なかった医学研究をより正確かつ効率的に行うことが可能になると期待される。
さらに、本国際共同研究の実施により、米ハーバード大やスイスETH Zurichなど、世界有数の研究機関の研究者とのネットワークが形成された。このネットワークは、国際学術誌Micromachinesのthematic issueの共同刊行や国際学会での招待講演の実施などの形で、既に本国際共同研究の枠組みを超えて学問領域の発展に貢献しつつある。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (22 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (12 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Harvard University(米国)2018

    • Year and Date
      2018-07-31
    • Related Report
      2020 Annual Research Report
  • [Journal Article] Systematic Understanding of Pathophysiological Mechanisms of Oxidative Stress-Related Conditions?Diabetes Mellitus, Cardiovascular Diseases, and Ischemia?Reperfusion Injury2021

    • Author(s)
      Wang Mengxue, Liu Yun, Liang Yin, Naruse Keiji, Takahashi Ken
    • Journal Title

      Frontiers in Cardiovascular Medicine

      Volume: 8 Pages: 649785-649785

    • DOI

      10.3389/fcvm.2021.649785

    • NAID

      120007037390

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of the TRPM4 channel in mitochondrial function, calcium release, and ROS generation in oxidative stress2021

    • Author(s)
      Wang Chen, Chen Jian, Wang Mengxue, Naruse Keijij, Takahashi Ken
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: accepted

    • NAID

      120007099346

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Model of Ischemic Heart Disease and Video-Based Comparison of Cardiomyocyte Contraction Using hiPSC-Derived Cardiomyocytes2020

    • Author(s)
      Liu Yun, Liang Yin, Wang Mengxue, Wang Chen, Wei Heng, Naruse Keiji, Takahashi Ken
    • Journal Title

      Journal of Visualized Experiments

      Volume: - Issue: 159

    • DOI

      10.3791/61104

    • NAID

      120006872429

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a model of ischemic heart disease using cardiomyocytes differentiated from human induced pluripotent stem cells2019

    • Author(s)
      Wei Heng、Wang Chen、Guo Rui、Takahashi Ken、Naruse Keiji
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 520 Issue: 3 Pages: 600-605

    • DOI

      10.1016/j.bbrc.2019.09.119

    • NAID

      120006795604

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of the TRPM4 Channel in Cardiovascular Physiology and Pathophysiology2018

    • Author(s)
      Wang C, Naruse K, Takahashi K
    • Journal Title

      Cells

      Volume: 7(6) Issue: 6 Pages: 62-62

    • DOI

      10.3390/cells7060062

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Human gingival fibroblast feeder cells promote maturation of induced pluripotent stem cells into cardiomyocytes2018

    • Author(s)
      Matsuda Y, Takahashi K, Kamioka H, Naruse K
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 503(3) Issue: 3 Pages: 1798-1804

    • DOI

      10.1016/j.bbrc.2018.07.116

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Establishing an artificial heart model on a chip by using cardiomyocytes2021

    • Author(s)
      Wang Mengxue, Yun Liu, Kenji Naruse, Ken Takahashi
    • Organizer
      The 98th Annual Meeting of The Physiological Society of Japan
    • Related Report
      2020 Annual Research Report
  • [Presentation] Optimization of the cardiac differentiation of human pluripotent stem cells2021

    • Author(s)
      Liu Yun, Mengxue Wang, Kenji Naruse, Ken Takahashi
    • Organizer
      The 98th Annual Meeting of The Physiological Society of Japan
    • Related Report
      2020 Annual Research Report
  • [Presentation] Kidney-on-a-chip model using human renal proximal tubular epithelial cells and human umbilical vein endothelial cells2021

    • Author(s)
      Yin Liang, Mengxue Wang, Keiji Naruse, Ken Takahashi
    • Organizer
      The 98th Annual Meeting of The Physiological Society of Japan
    • Related Report
      2020 Annual Research Report
  • [Presentation] Development of microfluidic cell culture system in preparation for human organ on a chip2020

    • Author(s)
      高橋 賢, 王 梦雪, 劉 雲, 梁 茵, 王 晨, 成瀬 恵治
    • Organizer
      第59会日本生体医工学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ヒト臓器チップを用いた臓器機能評価2020

    • Author(s)
      高橋 賢
    • Organizer
      CBI学会2020年大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Ischemia-reperfusion injury2019

    • Author(s)
      Takahashi K
    • Organizer
      2019 International Conference for Leading and Young Medical Scientists
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Roles of the TRPM4 channel in mitochondrial function, ROS generation, and calcium release in myocardial ischemia-reperfusion injury2019

    • Author(s)
      Wang C, Naruse K, Takahashi K
    • Organizer
      2019 International Conference for Leading and Young Medical Scientists
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Roles of the TRPM4 channel in mitochondrial function, ROS generation, and calcium release in myocardial ischemia-reperfusion injury2019

    • Author(s)
      Wang C, Chen J, Naruse K, Takahashi K
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Mechanobiology and its application to medical problem solving2019

    • Author(s)
      Takahashi K
    • Organizer
      2019 International Conference on Biology and Medical Sciences
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Cellular model of ischemic heart disease using human induced pluripotent stem cells2018

    • Author(s)
      Wei H, Wang C, Takahashi K, Naruse K
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Effect of dimensional factor of cell culture on cardiac differentiation of human induced pluripotent stem cells2018

    • Author(s)
      Tada C, Takahashi K, Naruse K
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] TRPM4 channel is involved in cellular damage caused by simulated ischemia-reperfusion injury: study of human iPSC-derived cardiomyocytes2018

    • Author(s)
      Wang C, Wei H, Naruse K, Takahashi K
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2018 Research-status Report
  • [Remarks] KEN TAKAHASHI website

    • URL

      https://ken-takahashi.net/category/research/

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
  • [Remarks] 高橋賢の研究Blog

    • URL

      https://ken-takahashi.net/?cat=4

    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] 心筋細胞の作製方法2020

    • Inventor(s)
      高橋賢、出射明美、成瀬恵治
    • Industrial Property Rights Holder
      高橋賢、出射明美、成瀬恵治
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2019 Research-status Report

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Published: 2018-01-25   Modified: 2022-01-27  

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