Generation of Stable Chambered Cardioids from human Pluripotent Stem Cells [scRNA-seq]

The human heart is a vital organ under intense investigation for the hope to improve health and longevity. Recent advances to generate cardiac organoids (cardioids) provide unprecedented opportunities to cardiac research. However, achieving stable chambered cardioids structures remains a challenge, thus limiting its application in disease modeling and drug screening. In this study, we address this challenge by orchestrating cardiac signaling pathways, including synergistic modulation of FGF and Wnt signaling via the HAND1 transcription factor. We have successfully demonstrated the formation of stable chambered cardioids structured with endocardium, myocardium, and epicardium, mimicking early cardiac development with well-organized structural components. Furthermore, we demonstrate the feasibility to leverage this platform for drug toxicity screening. Our findings provide a system to understand human heart development and generate models for cardiac tissue engineering and regenerative medicine.