FLEXcyte 96 application note (0.6 MB)
Cardiosight-S® cardiomyocytes kindly provided by Nexel
In order to reduce cardiovascular safety liabilities of new therapeutic agents, there is an urgent need to integrate human-relevant platforms/approaches into drug development. Optimizing baseline function of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is essential for their effective application in models of cardiac toxicity and disease. Here, hiPSC-CMs were cultured on flexible substrates using the FLEXcyte 96 system. The pro-maturation environment enables observation of inotropic and chronotropic compound effects, which are typically hard to detect with 2D monolayers on overly stiff substrates. For example, the beta-adrenergic agonist isoprenaline, or isoproterenol, is well known for its positive inotropic effects on the human heart, although common hiPSC-CM in vitro assays fail to display this physiological response by this compound.
Sala et al. (2018) developed a method that allows for a comparison of cardiac contraction measurements derived from different measurement approaches. The method, called MUSCLEMOTION, builds on previously existing algorithms, is fully automated and can be used on videos, image stacks, or image sequences loaded in the open-source image-processing program ImageJ.It is an open-source, dynamic platform that can be expanded, improved, and integrated for customized applications. Dynamic changes in pixel intensity between image frames are determined and the output is expressed as a relative measure of movement during muscle contraction and relaxation. Here, we compare the previously depicted data sets from Sala et al. 2018 and compare it to FLEXcyte 96 data as recorded with Cardiosight-S® cardiomyocytes (Nexel).