Noninvasive analysis of contractile function of human iPS-derived cardiomyocytes

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K19499
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Pharmaceutical Sciences and related fields
• Research Institution: University of Shizuoka
• Principal Investigator: Kurokawa Junko 静岡県立大学, 薬学部, 教授 (40396982)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: 心毒性 / ヒトiPS細胞 / 品質評価

Outline of Final Research Achievements

In this study, we aimed to non-invasively identify the tissue-specific properties of human iPS cell-derived cardiomyocytes using motion vector analysis. We demonstrated that commercially available human iPS cell-derived cardiomyocytes have diverse properties by examining the contractile functions of cells that have been dyed by antibody immunostaining against an atrial muscle marker and a ventricular muscle marker. It was found that the contraction speed and relaxation speed of atrial-type was faster than those of ventricular-type. This result was in the same tendency as the difference observed in mouse atrial myocytes and ventricular myocytes, and there was a difference in the reactivity among different class of cardiovascular reagents. From the above, we have developed a novel experimental system that can non-invasively evaluate the drug actions.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究成果はヒトiPS細胞由来心筋細胞同株の細胞間における機能的ばらつきを定量的に評価できるようにしたことであり、基礎および応用研究に汎用されるヒトiPS細胞由来分化細胞の品質評価法を確立した点は学術的に意義が高い。
そして、ヒトiPS細胞を用いることで、これまで問題となっていた実験動物とヒトの違いから生じる非臨床試験と臨床でのギャップを埋め、不整脈や心不全などの重篤な副作用（心毒性）を新薬開発の非臨床段階で忌避する技術に応用できることが社会的意義である。