Scientific Reports · 29 authors, 3 centres
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This narrative review discusses the use of animal models and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for cardiac anti-arrhythmic drug discovery. The central conclusion is that animal models remain crucial for evaluating drug candidates and understanding arrhythmogenesis, while hiPSC-CMs offer valuable but limited human-relevant insights due to their immaturity.
This narrative review synthesizes evidence on the use of animal models and hiPSC-CMs for discovering and testing cardiac anti-arrhythmic drugs. It details the limitations of hiPSC-CMs, including immature ion current balances, impaired calcium handling, and suboptimal contraction compared to native human ventricular cardiomyocytes. The review emphasizes that while no single model perfectly replicates human arrhythmias, animal models—particularly genetically engineered mice, along with larger animals for preclinical studies—are indispensable for evaluating drug efficacy, safety, and underlying mechanisms. It concludes that future advances in therapy will likely come from integrating multiple modeling scales, from single cells to whole systems, rather than relying on a single approach. The primary limitation noted is the inherent species-specific differences in cardiac electrophysiology.
