Perspectives on the Use of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Biomedical Research

Cardiovascular disease is still a major cause of ill-health and mortality, heart failure and arrhythmia being among the causes of sudden cardiac death. There are few drugs available for treatment or prevention and it remains difficult to predict who will develop these conditions, even when disease-causing mutations or associated gene variants are identified in individuals or families. This is in part because widely used rodent models may not fully capture the physiology of the human heart. The advent of pluripotent stem cell technology that allows cardiovascular cells to be derived from patients and healthy individuals, in some cases genetically matched through mutation repair, is leading to paradigm shifts in how cardiovascular diseases are studied in humans. However, these cells are often only partially mature imposing some limitations in use. This Perspective reviews aspects of recent advances but also remaining challenges.
Christine Mummery provides a Perspective on applications of human iPSC-cardiomyocytes for disease modeling and drug testing, including recently developed advanced 3D-engineered cultures and multicellular formats enhancing the maturity of cardiomyocytes to rapidly expand their utility in drug discovery and cardiotoxicity screens beyond effects on ion channels.