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 the necessary quantities and quality. 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 hiPSC-derived cardiomyocytes limit the study of drug effects on a few but physiologically relevant modes of action. This has spurred efforts to mature hiPSC-derived cardiomyocytes and develop more relevant cardiac 3D models and in vitro assays for improved cardiac translational research.