The roles of human induced pluripotent stem cell-derived cardiomyocytes in drug discovery: managing in vitro safety study expectations.

Human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) preparations are increasingly employed in Herein, the authors review the importance of understanding the functional characteristics of the evolving spectrum of simpler (2D) and more complex (co-cultures, 3D constructs, and engineered tissues) human-derived cardiac preparations, and how their performance may be evaluated based on analytical sensitivity, variability, and reproducibility in order to correctly match preparations with expectations of different safety assays. The need for consensus clinical examples of electrophysiologic, contractile, and structural cardiotoxicities essential for benchmarking human-derived models is also discussed. It is helpful (but not essential) that hiPSC-CMs preparations fully recapitulate pharmacological responses of native adult human ventricular myocytes when evaluating cardiotoxicity