iPSC-Derived Cardiomyocytes for Patient-Specific Drug Response Profiling

Background: Interindividual variability in cardiac drug response and susceptibility to cardiotoxicity remains a major challenge in pharmacotherapy and precision medicine. Traditional preclinical models fail to capture patient-specific genetic backgrounds and often lack predictive power for human cardiac physiology. Induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) provide a transformative platform to model human myocardial function in vitro and enable personalized drug screening. These cells retain the genetic signature of the donor and exhibit key electrophysiological, contractile, and pharmacological properties relevant to patient-specific risk stratification. Methods and Results: This review summarizes current methodologies for generating iPSC-CMs and their application in pharmacological profiling. iPSCs are reprogrammed from patient somatic cells and differentiated into functional cardiomyocytes through stepwise modulation of developmental signaling pathways. High-content assays including multi-electrode arrays, calcium flux imaging, and automated contractility measurements are used to assess drug-induced changes in action potential duration, repolarization reserve, and arrhythmic potential. Patient-specific iPSC-CMs have been employed to uncover genotype-dependent drug responses in long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and dilated cardiomyopathy. Integration with CRISPR-based genome editing enables mechanistic dissection of drug-gene interactions and validation of pathogenic variants. Platforms combining iPSC-CMs with high-throughput screening and artificial intelligence are emerging to optimize dose selection and reduce cardiotoxicity in early drug development. Conclusion: iPSC-derived cardiomyocytes offer a patient-relevant, scalable, and mechanistically insightful model for predicting individual cardiac drug responses.