Proarrhythmia risk prediction using human induced pluripotent stem cell-derived cardiomyocytes

Publication date: April 2018Source: Journal of Pharmacological Sciences, Volume 136, Issue 4Author(s): Daiju Yamazaki, Takashi Kitaguchi, Masakazu Ishimura, Tomohiko Taniguchi, Atsuhiro Yamanishi, Daisuke Saji, Etsushi Takahashi, Masao Oguchi, Yuta Moriyama, Sanae Maeda, Kaori Miyamoto, Kaoru Morimura, Hiroki Ohnaka, Hiroyuki Tashibu, Yuko Sekino, Norimasa Miyamoto, Yasunari KandaAbstractHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are expected to become a useful tool for proarrhythmia risk prediction in the non-clinical drug development phase. Several features including electrophysiological properties, ion channel expression profile and drug responses were investigated using commercially available hiPSC-CMs, such as iCell-CMs and Cor.4U-CMs. Although drug-induced arrhythmia has been extensively examined by microelectrode array (MEA) assays in iCell-CMs, it has not been fully understood an availability of Cor.4U-CMs for proarrhythmia risk. Here, we evaluated the predictivity of proarrhythmia risk using Cor.4U-CMs. MEA assay revealed linear regression between inter-spike interval and field potential duration (FPD). The hERG inhibitor E−4031 induced reverse-use dependent FPD prolongation. We next evaluated the proarrhythmia risk prediction by a two-dimensional map, which we have previously proposed. We determined the relative torsade de pointes risk score, based on the extent of FPD with Fridericia's correction (FPDcF) change and early afterdepolariz...
Source: Journal of Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research