Recapitulating the growth of the human heart to mature cardioids

Objective

Cardiovascular disease (CVD) is the leading global cause of death. Yet, breakthroughs in cardiac therapies are limited due to the poor predictive power of current models. While the animals fail to accurately replicate human heart physiology, the human pluripotent stem cell-derived models remain underdeveloped and immature for reliable disease modeling and therapy development. To address these challenges, we propose to further develop our cardiac organoid (“cardioid”) model and recapitulate the key stages of heart growth, including trabeculation, compaction, vascularization, and postnatal hypertrophy, resulting in physiological-like maturation. We hypothesize that these processes lead synergistically to postnatal heart maturation. Guided by developmental principles, we will combine signaling, metabolic, and genetic manipulations, as well as quantitative morphometric, functional, and molecular readouts on our high throughput cardioid platform. By leveraging advanced technologies (e.g., light sheet microscopy and single-cell proteomics), we will develop a physiologically relevant cardiac model that enables predictive cardiac disease modeling and drug discovery, paving the way for innovative therapies and regenerative medicine.