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.

Immunosuppressants Tacrolimus and Sirolimus revert the cardiac antifibrotic properties of p38-MAPK inhibition in 3D-multicellular human iPSC-heart organoids

“…Our model will also contribute to building a 3D system that describes and interrogate the establishment of those developmental programs and mechanisms of fibrosis activation, providing inroads for ectopic manipulation to control the adverse effects of cardiac fibrosis in disease, a maladaptive process with associated morbidity and mortality. We acknowledge the limitations of this study since in vitro human cardiac models are complementary tools allowing mechanistic interrogation in an over-reductionist way (Thomas et al, 2022). Among these complementary tools, a finely-tuned integration of 3D-biomaterials-based methods, 3D-bioprinting, Human Engineered heart tissues (EHTs/muscle), micro-tissues, and MPSs sensors in combination with vascularized heart organoids and 2D cultures based on hiPSC-derived cardiomyocytes differentiation will provide insightful progress in the field of precision medicine and cardiac disease modeling (Cho et al, 2022).…”