We produce fully functional, non-transformed hPSC-CMs at a level of purity greater than 90% and with normal ratios of all important cardiac cell types. In addition to normal expression all of the key ion channels of the human heart (calcium, potassium, and sodium) and various cardiomyocytic markers of the human heart, our CardioSafe 3D cardiac toxicity assays screen for both direct cardiomyocyte cytotoxicity and arrhythmogenesis (or development of irregular beating patterns). We believe CardioSafe 3D is sensitive, stable, reproducible and capable of generating data enabling a more accurate prediction of the in-vivo cardiac effects of NCEs than is possible with existing preclinical testing systems, particularly the hERG assay.
We believe the clinical predictivity of the hERG assay is limited because it assesses only a single cardiac ion channel - the hERG potassium ion channel. It does not assess any other clinically relevant cardiac ion channels, including calcium, non-hERG potassium, and sodium ion channels. Also, importantly, the hERG assay does not assess the normal interaction between these ion channels and their regulators. In addition, the hERG assay does not assess clinically relevant cardiac biological effects associated with cardiomyocyte viability, including apoptosis and other forms of cytotoxicity, as well as energy, mitochondria, and oxidative stress. As a result of its limitations, results of the hERG assay can lead to false negative and false positive predictions regarding the cardiac safety of new drug candidates.