Induced pluripotent stem cell (iPSC)-based cardiac regenerative medicine requires the efficient generation, structural soundness and proper functioning of mature cardiomyocytes, derived from the patient's somatic cells. The most important functional property of cardiomyocytes is the ability to contract. Currently available methods routinely used to test and quantify cardiomyocyte function involve techniques that are labor-intensive, invasive, require sophisticated instruments or can adversely affect cell vitality. We recently developed optical flow imaging method analyses and quantified cardiomyocyte contractile kinetics from video microscopic recordings without compromising cell quality. Specifically, our automated particle image velocimetry (PIV) analysis of phase-contrast video images captured at a high frame rate yields statistical measures characterizing the beating frequency, amplitude, average waveform and beat-to-beat variations. Thus, it can be a powerful assessment tool to monitor cardiomyocyte quality and maturity. Here we demonstrate the ability of our analysis to characterize the chronotropic responses of human iPSC-derived cardiomyocytes to a panel of ion channel modulators and also to doxorubicin, a chemotherapy agent with known cardiotoxic side effects. We conclude that the PIV-derived beat patterns can identify the elongation or shortening of specific phases in the contractility cycle, and the obtained chronotropic responses are in accord with known clinical outcomes. Hence, this system can serve as a powerful tool to screen the new and currently available pharmacological compounds for cardiotoxic effects.

中文翻译：

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人iPSC衍生的心肌细胞的无操纵性培养为心脏毒性提供了一种新颖的筛选方法。

基于诱导多能干细胞（iPSC）的心脏再生医学需要有效生成，结构健全和正常运作的，源自患者体细胞的成熟心肌细胞。心肌细胞最重要的功能特性是收缩能力。目前常规用于测试和量化心肌细胞功能的可用方法包括劳动密集型，有创性，需要精密仪器或可能对细胞活力产生不利影响的技术。我们最近开发了光流成像方法分析，并在不影响细胞质量的前提下从视频显微镜记录中量化了心肌细胞的收缩动力学。具体来说，我们对以高帧频捕获的相衬视频图像进行自动粒子图像测速（PIV）分析，得出了统计指标，可表征跳动频率，幅度，平均波形和逐拍变化。因此，它可以成为监测心肌细胞质量和成熟度的强大评估工具。在这里，我们证明了我们的分析能力能够表征人iPSC衍生的心肌细胞对一系列离子通道调节剂以及对阿霉素（具有已知心脏毒性副作用的化疗药物）的变时反应。我们得出的结论是，PIV衍生的搏动模式可以识别收缩周期中特定阶段的延长或缩短，并且获得的变时性反应与已知的临床结果一致。因此，