Unleashing Potential: First Vietnamese 3D in vitro Model using Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Abstract

Advancements in studying cardiovascular diseases (CVDs) face challenges related to cell sources and utilizing animal models. To mitigate these limitations, three-dimensional (3D) in vitro modeling using human induced pluripotent stem cell-derived cardiomyocytes (iCMs) has emerged as a promising approach. In this study, human induced pluripotent stem cells (hiPSCs) were successfully differentiated into cardiomyocytes and subsequently used to generate spheroids via the hanging drop method. We comprehensively characterized the formation, fusion, and beating capability of the generated spheroids. The hiPSCs were efficiently differentiated into cardiomyocytes, exhibiting contractile activity and expressing cardiac-specific markers such as α-actinin and cardiac troponin. Subsequent results demonstrated the successful formation of iCM-derived cardiac spheroids within 48 hours, with beating activity observed after two days cultured in an ultra-low attachment 96-well plate. In addition, similar to the iCM monolayer, the established spheroids also positively expressed α-actinin. Notably, the spheroids exhibited rapid assembly and maintained survival and stable beating throughout the observation period. These findings highlight the potential of establishing a robust in vitro iCM-derived 3D spheroids model for drug testing and cardiovascular disease modeling, typically for Vietnamese people.