On-chip in vitro cell-network pre-clinical cardiac toxicity using spatiotemporal human cardiomyocyte measurement on a chip

Tomoyuki Kaneko, Fumimasa Nomura, Tomoyo Hamada, Yasuyuki Abe, Hideo Takamori, Tomoko Sakakura, Kiyoshi Takasuna, Atsushi Sanbuissho, Johan Hyllner, Peter Sartipy, Kenji Yasuda*

*この研究の対応する著者

研究成果: Article査読

40 被引用数 (Scopus)

抄録

To overcome the limitations and misjudgments of conventional prediction of arrhythmic cardiotoxicity, we have developed an on-chip in vitro predictive cardiotoxicity assay using cardiomyocytes derived from human stem cells employing a constructive spatiotemporal two step measurement of fluctuation (short-term variability; STV) of cell's repolarization and cell-to-cell conduction time, representing two origins of lethal arrhythmia. Temporal STV of field potential duration (FPD) showed a potential to predict the risks of lethal arrhythmia originated from repolarization dispersion for false negative compounds, which was not correctly predicted by conventional measurements using animal cells, even for non-QT prolonging clinical positive compounds. Spatial STV of conduction time delay also unveiled the proarrhythmic risk of asynchronous propagation in cell networks, whose risk cannot be correctly predicted by single-cell-based measurements, indicating the importance of the spatiotemporal fluctuation viewpoint of in vitro cell networks for precise prediction of lethal arrhythmia reaching clinical assessment such as thorough QT assay.

本文言語English
論文番号4670
ジャーナルScientific reports
4
DOI
出版ステータスPublished - 2014 4月 22
外部発表はい

ASJC Scopus subject areas

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