Human iPSC-derived heart valve-like assembloids model valve development and disease pathology.

Heart valves maintain unidirectional blood flow, yet most understanding of their development and disease comes from animal models that do not fully capture human valve behavior. We present a human induced pluripotent stem cell (iPSC)-derived valve-like assembloid platform that models key aspects of in vivo valve features at the cellular and molecular levels. We found that mechanical forces, endothelial culture conditions, and fluidic shear stress respectively promote valve induction, maintenance, and extracellular matrix stratification. We further used this system to model human valve defects, including genetic mutations, injury, and hyperglycemia-related abnormalities. This assembloid platform enables the in vitro study of human valve development and disease mechanisms.