Use of Human Induced Pluripotent Stem Cells for Predicting Diverse Cardiotoxicities

Accurately predicting cardiotoxicity and elucidating the underlying mechanisms remain vexing and expensive problems for drug discovery. This is due, in part, to the wide range of causes and manifestations. Ion-channel block can lead to acute and delayed arrhythmias, while biochemical toxicities can result in cell death, abnormal cardiac function, and even heart failure and death. Finding physiologically relevant, reproducible, and reliable cell models that can be used to detect these end points at preclinical and discovery stages has been a challenge, as most toxicity testing is done either by using immortalized cancer cell lines, primary explanted somatic cells, or live animals. The development of human induced pluripotent stem cell (iPSC)-derived cell lines as models for drug-toxicity testing offers a promising alternative that is more physiologically relevant, more predictive, and more time and cost efficient. Although iPSC-derived cardiomyocytes have not yet replaced well-established FDA-approved toxicological methods, the FDA has fast-tracked efforts ...