Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs) in Translational Research: Current Landscape, Clinical Applications, and Future Paradigms
DOI:
https://doi.org/10.67224/ioasdjmps.2026.v03i02.003Keywords:
hiPSC-CMs, Cardiovascular Disease Modeling, Cardiotoxicity Screening, Regenerative Medicine, CiPA Initiative, CRISPR/Cas9, Long QT SyndromeAbstract
The advent of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represents a paradigm shift in cardiovascular research, overcoming the physiological limitations of animal models and the scarcity of primary human tissues. This review provides a comprehensive analysis of the role of hiPSC-CMs in translational research, emphasizing their transformative applications in disease modeling, drug discovery, and regenerative medicine. We examine methodologies for generating high-purity cardiomyocytes, particularly through the biphasic modulation of Wnt signaling pathways, and evaluate advanced biochemical, mechanical, and electrical techniques for driving cellular maturation. The critical need for reproducibility in high-throughput environments is addressed through an assessment of standardized platforms, which facilitate robust regulatory compliance. Furthermore, this review highlights the advantages of hiPSC-CMs in preserving authentic human genetic backgrounds and leveraging CRISPR/Cas9 technology to generate isogenic controls for precision medicine. Despite rapid advancements, persistent limitations—most notably the fetal-like immature phenotype, cellular heterogeneity, and In vivo arrhythmogenic risks—remain substantial hurdles. Through detailed case studies on Long QT Syndrome and Doxorubicin-induced cardiotoxicity, we illustrate the practical efficacy of these in vitro models. Finally, we discuss recent milestones, including engineered heart muscle (EHM) patches and the regulatory integration of hiPSC-CM data via the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative, underscoring the trajectory of hiPSC-CMs toward realizing personalized cardiovascular medicine.
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Copyright (c) 2026 Sankaramanivel Sundararaj, Karthik Rajendran, Amit Khanna (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
