Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes in the Evaluation of Cardiotoxic Potential of Drugs

  • Yee Xiang ChangEmail author
  • Christine L. Mummery


Drug development process is currently a lengthy and costly process. One contributing factor to the high cost of drugs is the expense of failed products. To address this problem, early detection of potentially harmful drugs is important so that their development does not advance into expensive clinical trials and then fail to get regulatory approval. Drugs that cause heart damage are among those most commonly removed from the market. Current in vitro safety pharmacology screenings only focus on the evaluation of drug-induced QT prolongation or torsade des pointes (TdP) risks by examining individual cardiac ion channel currents or the action potential. These screenings are oversimplified, resulting in inaccurate prediction, high drug attrition rates, and drug withdrawals from the market. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are promising models for cardiotoxicity screening as some human cardiomyocyte features are recapitulated and disease- and patient-specific lines can be generated. The new generation of iPSCs has solved the problem of inefficient cardiomyocyte differentiation and provides optimism in the application of hiPSC-CMs in cardiotoxicity screening. In this chapter, an overview is given of safety pharmacological assays evaluating hiPSC-CM function, and the validity of the application of hiPSC-CM models in cardiotoxicity screening will be assessed.


Human pluripotent stem cells Cardiomyocyte differentiation Cardiac disease Drug discovery Cardiac arrhythmia 



Action potential


Action potential amplitude


Action potential duration




Calcium-sensitive detector


Half maximal effective concentration


Extracellular acidification rate




Engineered heart tissue


Embryonic stem cell


Food and Drug Administration


Field potential


Field potential amplitude


Field potential duration

HEK-293 cells

Human embryonic kidney 293 cells


Human Ether-à-go-go-Related Gene


Human-induced pluripotent stem cell-derived cardiomyocyte


Half maximal inhibition concentration


The International Council on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use


Inward-rectifier K+ current


Induced pluripotent stem cell


Interspike interval


Multielectrode arrays


New chemical entities


Oxygen consumption rate


Torsade de pointes


Maximal upstroke velocity


Voltage-sensitive dye


Extracellular flux



We thank Dr. Joost O. Fledderus from the University Medical Center Utrecht for his expertise and comments that improved the manuscript. In addition, we apologize to all those authors whose excellent work could not be cited due to space restrictions.


C.L.M. is a cofounder of Pluriomics B.V.


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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.University of UtrechtUtrechtThe Netherlands
  2. 2.Department of Anatomy and EmbryologyLeiden University Medical CentreLeidenThe Netherlands

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