2020 Fiscal Year Final Research Report
Development of electrophysiological indices to predict proarrhythmic risk of a drug in a human iPS cell-derived cardiomyocytes' sheet through its functional characterization
| Project/Area Number |
17K08608
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Toho University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Keywords | ヒトiPS細胞由来心筋細胞 / 多電極システム / 催不整脈性 / 抗不整脈性 / イオンチャネル / モーションベクトル |
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| Outline of Final Research Achievements |
In this project, I developed electrophysiological indices for human iPS cell-derived cardiomyocytes’ monolayer sheets to outline the pro- and/or anti-arrhythmic properties of drugs. Each cell sheet was prepared on each microelectrode-array probe, and then paced with programmed stimuli via a pair of adjacent electrodes before and after drug treatment. I examined the electrophysiological indices of the cell sheet for detecting Na+ channel blockade with its characteristics, blockade of K+ and Ca2+ channels, and their balance in the repolarization phase using clinical antiarrhythmics. I then assessed an anticancer agent and a Kampo preparation with the indices and detected their multichannel blocking actions. The obtained results indicated that the cell sheets with the indices could be valuable to predict pro- and/or anti-arrhythmic action of a substance in the human intact heart.
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| Free Research Field |
電気薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
多くの薬物が主作用の他に、心臓のイオンチャネルを修飾し、その結果、催不整脈性や抗不整脈性を持つことが明らかになっており、その作用を見極めることは大変重要である。ヒトiPS心筋細胞はヒトの生体心と同じイオンチャネルを発現しているので、この細胞を使用して催不整脈性や抗不整脈性を正確に評価できれば、種差もなく、ヒト生体心へその結果を外挿することが出来る。本研究では2 mm四方のヒトiPS細胞由来心筋細胞シートに多電極システムと電気刺激を組み合わせることにより、複数のイオンチャネル遮断作用をもつ薬物であっても催不整脈性や抗不整脈性の概要が把握できる電気生理学的指標を開発した。
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