Identification of Ion Currents Components Generating Field Potential Recorded in MEA From hiPSC-CM
Identification of Ion Currents Components Generating Field Potential Recorded in MEA From hiPSC-CM
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DOI：
10.1109/tbme.2017.2748798
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发表时间：
2018-06-01
影响因子：
4.6
通讯作者：
Gerbeau, Jean-Frederic
中科院分区：
文献类型：
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作者：
Raphel, Fabien;Boulakia, Muriel;Gerbeau, Jean-Frederic
目的：多电极阵列(MEAs)与人诱导多能干细胞来源的心肌细胞(hiPSC-CMS)相结合，可实现高通量或中通量的药物安全药理学筛选。这项技术最近引起了很多关注，特别是来自一项名为CIPA的国际倡议。但目前它受到测量信号分析难度的限制。我们提出了一种分析MEA采集的信号并自动推断受药物影响的通道的策略。方法：我们的方法基于Biomain方程、MEA电极模型和反问题策略。结果：获得了两种商用设备的MEA信号，并给出了一个早期后去极化的例子。然后，通过处理四种不同化合物的真实信号，我们的算法能够提供钾、钠和钙通道的剂量-反应曲线。对于伊夫拉定和莫西沙星，其IC50和剂量-反应曲线与已知值非常吻合。意义：拟议的策略为安全药理学社区提出的一个主要问题提供了可能的答案。通过允许对信号进行更自动化的分析，我们的方法可以促进基于MEA和hiPSC-CMS的技术的推广，从而提高药物筛选的可靠性和效率。
Objective: Multi electrodes arrays (MEAs) combined with cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) can enable high-or medium-throughput drug screening in safety pharmacology. This technology has recently attracted a lot of attention, in particular from an international initiative named CiPA. But it is currently limited by the difficulty to analyze the measured signals. We propose a strategy to analyze the signals acquired by the MEA and to automatically deduce the channels affected by the drug. Methods: Our method is based on the bidomain equations, a model for the MEA electrodes, and an inverse problem strategy. Results: in silico MEA signals are obtained for two commercial devices and an example of early after depolarization is presented. Then, by processing real signals obtained for four different compounds, our algorithm was able to provide dose-response curves for potassium, sodium, and calcium channels. For ivabradine and moxifloxacin, the IC50 and dose-response curves are in very good agreement with known values. Significance: The proposed strategy offers a possible answer to a major question raised by the community of safety pharmacology. By allowing a more automated analysis of the signals, our approach could contribute to promote the technology based on MEA and hiPSC-CMs and, therefore, improve reliability and efficiency of drug screening.