Dhienda C. Shahannaz, Tadahisa Sugiura, Brandon E. Ferrell, Taizo Yoshida
Background and Objectives: Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have revolutionized cardiac research by providing patient-specific models for studying arrhythmias. However, their clinical application is hindered by arrhythmogenic risks associated with grafted iPSC-CMs. This review aims to delineate the current limitations in iPSC-CM-based arrhythmia modeling and explore emerging therapeutic strategies to mitigate these risks. Materials and Methods: A comprehensive literature review was conducted, focusing on studies published in the last two decades that address the electrophysiological characteristics of iPSC-CMs, their arrhythmogenic potential, and therapeutic interventions. Sources include peer-reviewed journals, clinical trial reports, and recent advancements in stem cell technology. Results: Findings indicate that while iPSC-CMs offer a promising platform for arrhythmia modeling, challenges such as cellular heterogeneity, immaturity, and proarrhythmic potential persist. Advancements in maturation protocols, co-culture systems, and gene editing techniques have shown promise in enhancing the safety profile of iPSC-CMs. Conclusions: Addressing the arrhythmogenic risks associated with iPSC-CMs requires a multifaceted approach, including improved differentiation protocols, maturation strategies, and therapeutic interventions. Continued research is essential to translate these models into safe and effective clinical applications.