Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes as an in vitro model in toxicology: strengths and weaknesses for hazard identification and risk characterization

Introduction Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes is one of the most widely used cell-based models that resulted from the discovery of how non-embryonic stem cells can be differentiated into multiple cell types. In just one decade, iPSC-derived cardiomyocytes went from a research lab to widespread use in biomedical research and preclinical safety evaluation for drugs and other chemicals. Areas covered This manuscript reviews data on toxicology applications of human iPSC-derived cardiomyocytes. We detail the outcome of a systematic literature search on their use (i) in hazard assessment for cardiotoxicity liabilities, (ii) for risk characterization, (iii) as models for population variability, and (iv) in studies of personalized medicine and disease. Expert opinion iPSC-derived cardiomyocytes are useful to increase the accuracy, precision, and efficiency of cardiotoxicity hazard identification for both drugs and non-pharmaceuticals, with recent efforts beginning to demonstrate their utility for risk characterization. Notable limitations include the needs to improve the maturation of cells in culture, to better understand their potential use identifying structural cardiotoxicity, and for additional case studies involving population-wide and disease-specific risk characterization. Ultimately, the greatest future benefits are likely for non-pharmaceutical chemicals, filling a critical gap where no routine testing for cardiotoxicity is currently performed.

Automated summary

iPSC-derived cardiomyocytes are valuable in improving the accuracy, precision, and efficiency of cardiotoxicity hazard identification for drugs and non-pharmaceuticals. Efforts are underway to demonstrate their utility in risk characterization, but challenges remain in cell maturation, understanding their use in identifying structural cardiotoxicity, and expanding case studies for population-wide and disease-specific risk characterization. Ultimately, iPSC-derived cardiomyocytes have great potential for enhancing cardiotoxicity testing for non-pharmaceutical chemicals.