Division of Pharmacology, National Institute of Health Sciences, 3-25-26, Tonomachi, Kawasaki-ku, Kanagawa 210-9501, Japan.
Division of Pharmacology, National Institute of Health Sciences, 3-25-26, Tonomachi, Kawasaki-ku, Kanagawa 210-9501, Japan; Division of Pharmaceutical Sciences, Graduated School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1, Tsushima-naka, kita-ku, Okayama, Okayama 700-8530, Japan.
J Pharmacol Toxicol Methods. 2022 Nov-Dec;118:107227. doi: 10.1016/j.vascn.2022.107227. Epub 2022 Oct 13.
Predicting drug-induced cardiotoxicity during the non-clinical stage is important to avoid severe consequences in the clinical trials of new drugs. Human iPSC-derived cardiomyocytes (hiPSC-CMs) hold great promise for cardiac safety assessments in drug development. To date, multi-electrode array system (MEA) has been a widely used as a tool for the assessment of proarrhythmic risk with hiPSC-CMs. Recently, new methodologies have been proposed to assess in vitro contractility, such as the force and velocity of cell contraction, using hiPSC-CMs. Herein, we focused on an imaging-based motion vector system (MV) and an electric cell-substrate impedance sensing system (IMP). We compared the output signals of hiPSC-CMs from MV and IMP in detail and observed a clear correlation between the parameters. In addition, we assessed the effects of isoproterenol and verapamil on hiPSC-CM contraction and identified a correlation in the contractile change of parameters obtained with MV and IMP. These results suggest that both assay systems could be used to monitor hiPSC-CM contraction dynamics.
在非临床阶段预测药物引起的心脏毒性对于避免新药临床试验中的严重后果非常重要。人诱导多能干细胞衍生的心肌细胞（hiPSC-CMs）在药物开发的心脏安全性评估中具有很大的潜力。迄今为止，多电极阵列系统（MEA）已被广泛用作评估 hiPSC-CMs 致心律失常风险的工具。最近，已经提出了新的方法来评估体外收缩性，例如使用 hiPSC-CMs 测量细胞收缩的力和速度。在这里，我们专注于基于成像的运动向量系统（MV）和电细胞-底物阻抗感应系统（IMP）。我们详细比较了 MV 和 IMP 中 hiPSC-CMs 的输出信号，观察到参数之间存在明显的相关性。此外，我们评估了异丙肾上腺素和维拉帕米对 hiPSC-CM 收缩的影响，并发现 MV 和 IMP 获得的参数的收缩变化之间存在相关性。这些结果表明，这两种测定系统都可用于监测 hiPSC-CM 的收缩动力学。
