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

2020 Fiscal Year Final Research Report

• Project/Area Number: 17KK0168
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Okayama 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
• 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

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.

Free Research Field

臓器チップ、生体医工学、循環器生理学

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。