AnaBios Corporation;
AnaBios Corporation.
J Vis Exp. 2022 Aug 9(186). doi: 10.3791/64394.
The evaluation of changes in heart contractility is essential during preclinical development for new cardiac- and non-cardiac-targeted compounds. This paper describes a protocol for assessing changes in contractility in adult human primary ventricular cardiomyocytes utilizing the MyoBLAZER, a non-invasive optical method that preserves the normal physiology and pharmacology of the cells. This optical recording method continuously measures contractility transients from multiple cells in parallel, providing both medium-throughput and valuable information for each individual cell in the field of view, enabling the real-time tracking of drug effects. The cardiomyocyte contractions are induced by paced electrical field stimulation, and the acquired bright field images are fed to an image-processing software that measures the sarcomere shortening across multiple cardiomyocytes. This method rapidly generates different endpoints related to the kinetics of contraction and relaxation phases, and the resulting data can then be interpreted in relation to different concentrations of a test article. This method is also employed in the late stages of preclinical development to perform follow-up mechanistic studies to support ongoing clinical studies. Thus, the adult human primary cardiomyocyte-based model combined with the optical system for continuous contractility monitoring has the potential to contribute to a new era of in vitro cardiac data translatability in preclinical medical therapy development.
在临床前开发阶段，评估新的心脏和非心脏靶向化合物对心肌收缩力的影响至关重要。本文描述了一种利用 MyoBLAZER 评估成人原代人心室肌细胞收缩力变化的方案，该方法是非侵入性的光学方法，可保留细胞的正常生理学和药理学特性。这种光学记录方法可连续测量来自多个细胞的收缩力瞬变，为视野内的每个细胞提供高通量和有价值的信息，从而实现药物作用的实时跟踪。心肌细胞的收缩是通过 paced 电场刺激诱导的，获取的明场图像被馈送到图像处理软件中，该软件可测量多个心肌细胞的肌节缩短。该方法可快速生成与收缩和舒张相动力学相关的不同终点，并且可以根据测试物质的不同浓度来解释所得数据。该方法还在临床前开发的后期阶段用于进行后续的机制研究，以支持正在进行的临床研究。因此，基于成人原代心肌细胞的模型结合用于连续收缩力监测的光学系统，有可能为临床前医学治疗开发中的体外心脏数据可转化性开创一个新时代。
