An evidence appraisal of heart organoids in a dish and commensurability to human heart development in vivo

Abstract

Stem-cell derived in vitro cardiac models have provided profound insights into mechanisms in cardiac development and disease. Efficient differentiation of specific cardiac cell types from human pluripotent stem cells using a three-step Wnt signaling modulation has been one of the major discoveries that has enabled personalized cardiovascular disease modeling approaches. Generation of cardiac cell types follow key development stages during embryogenesis, they intuitively are excellent models to study cardiac tissue patterning in primitive cardiac structures. Here, we provide a brief overview of protocols that have laid the foundation for derivation of stem-cell derived three-dimensional cardiac models. Further this article highlights features and utility of the models to distinguish the advantages and trade-offs in modeling embryonic development and disease processes. Finally, we discuss the challenges in improving robustness in the current models and utilizing developmental principles to bring higher physiological relevance. In vitro human cardiac models are complimentary tools that allow mechanistic interrogation in a reductionist way. The unique advantage of utilizing patient specific stem cells and continued improvements in generating reliable organoid mimics of the heart will boost predictive power of these tools in basic and translational research.

Keywords: 3D platforms; Cardiac organoids; Cellular crosstalk; Stem cells.

Fig. 1

Embryoid body-like cardiac models. A schematic summary of feature-specific cardiac organoid models derived from human iPSCs. The figure highlights striking differences in in size, chamber and septation and tissue patterning between current cardiac organoid models and to its in vivo counterpart, thereby providing a premise for further innovation and optimization