Pluripotent stem cells as a platform for cardiac arrhythmia drug screening

Since the first demonstrations of the differentiation of pluripotent stem cells to produce functional human cellular models such as cardiomyocytes, the scientific community has been captivated [1, 2••, 3]. In the time since that seminal work, the field has been catapulted forward by the demonstration that adult somatic cells can be reprogrammed to an induced state of pluripotency [4••], and more recently by the development of efficient and sophisticated genome editing tools [5••, 6••, 7], which together afford a theoretically unlimited supply of relevant genetic disease models. In particular, many of the early successes with induced pluripotent stem cell technology have been realized with cardiac arrhythmia syndromes [8••, 9-15]. There is interest in applying stem cell models in large-scale screens to discover novel therapeutics or drug toxicities. This manuscript aims to discuss the potential role of hPSC-derived cardiomyocyte models in therapeutic arrhythmia screens and review recent advances in the field that bring us closer to this reality.