Advances in humanoid organoid-based research on inter-organ communications during cardiac organogenesis and cardiovascular diseases.

The intimate correlation between cardiovascular diseases and other organ pathologies, such as metabolic and kidney diseases, underscores the intricate interactions among these organs. Understanding inter-organ communications is crucial for developing more precise drugs and effective treatments for systemic diseases. While animal models have traditionally been pivotal in studying these interactions, human-induced pluripotent stem cells (hiPSCs) offer distinct advantages when constructing in vitro models. Beyond the conventional two-dimensional co-culture model, hiPSC-derived humanoid organoids have emerged as a substantial advancement, capable of replicating essential structural and functional attributes of internal organs in vitro. This breakthrough has spurred the development of multilineage organoids, assembloids, and organoids-on-a-chip technologies, which allow for enhanced physiological relevance. These technologies have shown great potential for mimicking coordinated organogenesis, exploring disease pathogenesis, and facilitating drug discovery. As the central organ of the cardiovascular system, the heart serves as the focal point of an extensively studied network of interactions. This review focuses on the advancements and challenges of hiPSC-derived humanoid organoids in studying interactions between the heart and other organs, presenting a comprehensive exploration of this cutting-edge approach in systemic disease research.