Modeling Human Heart Development and Congenital Defects Using Organoids: How Close Are We?

The emergence of human-induced Pluripotent Stem Cells (hiPSCs) has dramatically improved our understanding of human developmental processes under normal and diseased conditions. The hiPSCs have been differentiated into various tissue-specific cells in vitro, and the advancement in three-dimensional (3D) culture has provided a possibility to generate those cells in an in vivo-like environment. Tissues with 3D structures can be generated using different approaches such as self-assembled organoids and tissue-engineering methods, such as bioprinting. We are interested in studying the self-assembled organoids differentiated from hiPSCs, as they have the potential to recapitulate the in vivo developmental process and be used to model human development and congenital defects. Organoids of tissues such as those of the intestine and brain were developed many years ago, but heart organoids were not reported until recently. In this review, we will compare the heart organoids with the in vivo hearts to understand the anatomical structures we still lack in the organoids. Specifically, we will compare the development of main heart structures, focusing on their marker genes and regulatory signaling pathways.