Modeling early human heart development using an iPSC-based 3D bioprinted model of embryonic heart tube

Abstract

Human heart development depends on tightly coordinated genetic programs and biomechanical cues, yet the underlying cell–microenvironment interactions remain poorly understood because the developing heart is difficult to study in utero and accurate experimental models are lacking. Recent advances in stem cell biology and three dimensional (3D) bioprinting now allow the construction of human tissue analogues with defined structure and function. Here we show a perfusable 3D bioprinted model of the human embryonic heart tube composed of layered myocardium, cardiac jelly, and

endocardium. Human induced pluripotent stem cell–derived cardiomyocytes and endothelial cells are cultured under controlled flow conditions, producing constructs with high cell viability, complete lumen endothelialization, progressive myocardial compaction, and coordinated tissue-level contraction. Single-cell transcriptomic analysis reveals that dynamic flow promotes cardiac maturation and lineage specification. This platform provides a human-relevant model to study early heart development, investigate congenital heart disease mechanisms, and evaluate emerging therapeutic strategies.