High throughput measurement of Ca²⁺ dynamics for drug risk assessment in human stem cell-derived cardiomyocytes by kinetic image cytometry.
High throughput measurement of Ca²⁺ dynamics for drug risk assessment in human stem cell-derived cardiomyocytes by kinetic image cytometry.
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DOI：
10.1016/j.vascn.2012.08.167
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发表时间：
2012-11
影响因子：
1.9
通讯作者：
Mercola M
中科院分区：
文献类型：
--
作者：
Cerignoli F;Charlot D;Whittaker R;Ingermanson R;Gehalot P;Savchenko A;Gallacher DJ;Towart R;Price JH;McDonough PM;Mercola M
目前测量心肌细胞生理特性并预测可导致猝死的致命性心律失常（例如尖端扭转型室性心动过速）的方法缺乏早期药物发现所需的自动化和通量和/或预测价值较差。为了提高体外检测的通量和预测能力，我们开发了动力学成像细胞术 (KIC)，通过细胞内荧光 Ca2+ 指示剂进行自动逐个细胞分析。 KIC 仪器可在数秒内以 30 毫秒的分辨率同时记录和分析 96 孔板的数百个单个细胞/孔的细胞内钙浓度 [Ca2+]i，提供以前使用读板器等均值技术无法实现的动力学细节。对人胚胎干细胞和诱导多能干细胞衍生的心肌细胞的分析揭示了已知的心脏毒性和致心律失常药物对 Ca2+ 动力学动力学参数的影响，表明 KIC 将有助于评估心脏毒性风险，并有助于阐明与药物治疗和/或遗传背景相关的心脏病的致病机制。
Current methods to measure physiological properties of cardiomyocytes and predict fatal arrhythmias that can cause sudden death, such as Torsade de Pointes, lack either the automation and throughput needed for early-stage drug discovery and/or have poor predictive value. To increase throughput and predictive power of in vitro assays, we developed kinetic imaging cytometry (KIC) for automated cell-by-cell analyses via intracellular fluorescence Ca2+ indicators. The KIC instrument simultaneously records and analyzes intracellular calcium concentration [Ca2+]i at 30-ms resolution from hundreds of individual cells/well of 96-well plates in seconds, providing kinetic details not previously possible with well averaging technologies such as plate readers. Analyses of human embryonic stem cell and induced pluripotent stem cell-derived cardiomyocytes revealed effects of known cardiotoxic and arrhythmogenic drugs on kinetic parameters of Ca2+ dynamics, suggesting that KIC will aid in the assessment of cardiotoxic risk and in the elucidation of pathogenic mechanisms of heart disease associated with drugs treatment and/or genetic background.
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影响因子：
4.8
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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作者：
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DOI：
10.1016/j.vascn.2005.07.003
发表时间：
2006-03-01
影响因子：
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作者：
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