"Cardiovascular diseases (CVD) remain as the leading cause of death worldwide, and there is an increasing focus on developing physiologically relevant in vitro cardiovascular tissue models suitable for studying personalized medicine and pre-clinical tests. While recent technologies provide some insight into how human CVDs can be modelled in vitro, they may not always give a comprehensive overview of the complexity of the human heart due to their limits in cellular heterogeneity and physiological complexity. Furthermore, animal models may not always faithfully reflect the features that are unique to human biology and disease .
We have optimized a scaffold-free protocol to generate multicellular, beating, self-organized and functional human cardiac organoids (hCOs) derived in vitro from induced pluripotent stem cells (iPSCs). The hCOs contain multiple cell types of the heart, are viable for more than 50 days, and show functional beating response without external stimuli. We have shown that hCOs have improved cardiac specification, survival and maturation compared to standard 2D monolayer cardiac differentiation. Furthermore, the hCOs has shown functional beating response to cardioactive drugs, and could be used to model chemotherapy-induced cardiotoxicity. Our study demonstrates that culture dimensionality and time are important for survival, differentiation, and maturation of in vitro cardiac tissue models in long term, and could enable further possibilities in translational research in cardiovascular biology.
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