Success and Challenges with Models for Cardiac Translational Research

Human induced pluripotent stem cells (hiPSCs) are a significant milestone in modern biology. hiPSCs, being capable of differentiating into any cell type, provide access to all cell types of the human body at an almost infinite scale. This is particularly important for cells, such as human cardiomyocytes, that cannot be isolated from primary tissue in thenecessary quantitiesandquality. In a nine-year process, hiPSC-derived cardiomyocytes were successfully validated in several blinded multisite studies for their use in cardiac safety pharmacology and were finally included in the ICH guidelines. However, the immature properties of hiPSCderived cardiomyocytes limit the study of drug effects on a few but physiologically relevant modesof action. This has spurred efforts tomature hiPSC-derivedcardiomyocytesanddevelopmore relevant cardiac 3Dmodels and in vitro assays for improved cardiac translational research.