Quantitatively characterizing drug-induced arrhythmic contractile motions of human stem cell-derived cardiomyocytes.

Quantitatively characterizing drug-induced arrhythmic contractile motions of human stem cell-derived cardiomyocytes.
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DOI:
10.1002/bit.26709
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发表时间:
2018-08
影响因子:
3.8
通讯作者:
Jacquir S
Jacquir S
中科院分区:
工程技术2区
文献类型:
--
作者:
Hoang P;Huebsch N;Bang SH;Siemons BA;Conklin BR;Healy KE;Ma Z;Jacquir S

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心脏组织异常收缩运动的定量是评估和分类药物诱导的心律失常(即尖端扭转型室性心动过速)的一个值得注意的挑战和重大限制。为了克服这些挑战,研究人员利用计算机图像处理工具来测量来自人类诱导多能干细胞(hiPSC-CM)的心肌细胞的收缩运动。然而,收缩运动波形的幅度和频率分析不产生足够的信息来客观地分类两组或更多组心脏收缩运动之间的变化程度。在本文中,我们产生的收缩运动数据从跳动的hiPSC-CM使用基于光流分析的运动跟踪软件,然后实施了一种计算算法,相空间重建(PSR),推导参数(嵌入,规则性,分形维数),以进一步表征心脏收缩运动的动态性质。应用已知会导致心律失常的药物会导致PSR分析计算的这些合成尺寸参数发生显著变化。将这种新的计算算法与现有的心脏收缩运动分析工具箱相结合,将使我们能够将目前对心脏组织生理学的评估扩展为自动化、高通量和可量化的方式,这将允许对药物诱导的致心律失常进行更客观的评估。
Quantification of abnormal contractile motions of cardiac tissue has been a noteworthy challenge and significant limitation in assessing and classifying the drug-induced arrhythmias (i.e. Torsades de pointes). To overcome these challenges, researchers have taken advantage of computational image processing tools to measure contractile motion from cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs). However, the amplitude and frequency analysis of contractile motion waveforms doesn’t produce sufficient information to objectively classify the degree of variations between two or more sets of cardiac contractile motions. In this paper, we generated contractile motion data from beating hiPSC-CMs using motion tracking software based on optical flow analysis, and then implemented a computational algorithm, phase space reconstruction (PSR), to derive parameters (embedding, regularity, and fractal dimensions) to further characterize the dynamic nature of the cardiac contractile motions. Application of drugs known to cause cardiac arrhythmia induced significant changes to these resultant dimensional parameters calculated from PSR analysis. Integrating this new computational algorithm with the existing analytical toolbox of cardiac contractile motions will allow us to expand current assessments of cardiac tissue physiology into an automated, high-throughput, and quantifiable manner which will allow more objective assessments of drug-induced proarrhythmias.
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期刊: SCIENTIFIC REPORTS
影响因子: 4.6
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期刊: STEM CELL REPORTS
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DOI: 10.1016/j.stemcr.2014.09.017
发表时间: 2014-12-09
期刊: Stem cell reports
影响因子: 5.9
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DOI: 10.1103/physreve.58.6392
发表时间: 1998-11-01
期刊: PHYSICAL REVIEW E
影响因子: 2.4
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通讯作者: Schreiber, T