Cardiac electrophysiology evaluation system for improved drug assessment

2024 Fiscal Year Final Research Report

• Project/Area Number: 22K12801
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: Osaka University
• Principal Investigator: LI JUNJUN 大阪大学, 大学院工学研究科, 特任准教授(常勤) (10723786)
• Co-Investigator(Kenkyū-buntansha): 劉 莉 大阪大学, 大学院医学系研究科, 特任准教授 (50380093)
• Project Period (FY): 2022-04-01 – 2025-03-31
• Keywords: iPSC / Cardiomyocytes / Drug assessment / Tissue engineering

Outline of Final Research Achievements

In this study, stable traveling waves were successfully and efficiently reproduced in a 24-well plate using a newly designed device and were stably maintained for over 14 days. The maturation of iPSC-derived cardiomyocytes paced by the waves was confirmed through immunostaining, electrophysiological recording, RNA sequencing, TEM, OCR, western blotting, and motion analysis. Drug responses were evaluated using compounds with varying levels of Torsades de Pointes (TdP) risk: low-risk drugs (verapamil, ranolazine) showed low arrhythmia rates, while high- and intermediate-risk drugs (quinidine, pimozide) increased arrhythmia incidence, demonstrating the system’s utility in drug safety assessment. As outcomes, one PCT patent was filed, four papers were published, and one oral presentation was given at an conference. This presentation received the 21st Young Investigator’s Award for International Students.

Free Research Field

Tissue engineering; Regenerative medicine;

Academic Significance and Societal Importance of the Research Achievements

最近、FDAはモノクローナル抗体などの医薬品に対する動物実験の義務を段階的に廃止する方針を示しました。iPSC由来の心臓オルガノイドは動物実験の代替として期待され、薬剤毒性評価の新しいプラットフォームとなります。しかし、iPSC由来心筋細胞の未成熟性が薬剤応答の精度を制限する課題があります。我々のシステムは心筋細胞の成熟を促進し、より正確な薬剤応答を実現しました。これにより、PMDAによる偽陽性薬剤候補の誤却下を減らし、創薬の効率向上とコスト削減に貢献します。また、動物実験削減という倫理的課題にも応え、持続可能な医療社会の実現に寄与する技術です。