Multi-chamber cardioids unravel human heart development and cardiac defects

Abstract

The number one cause of human fetal death are defects in heart development. Because the human embryonic heart is inaccessible, and the impacts of mutations, drugs, and environmental factors on the specialized functions of different heart compartments are not captured by in vitro models, determining the underlying causes is difficult. Here, we established a human cardioid platform that recapitulates the development of all major embryonic heart compartments, including right and left ventricles, atria, outflow tract, and atrioventricular canal. By leveraging both 2D and 3D differentiation, we efficiently generated progenitor subsets with distinct first, anterior, and posterior second heart field identities. This advance enabled the reproducible generation of cardioids with compartment-specific in vivo-like gene expression profiles, morphologies, and functions. We used this platform to unravel the ontogeny of signal and contraction propagation between interacting heart chambers and dissect how genetic and environmental factors cause region-specific defects in the developing human heart.

Cardiopharyngeal Mesoderm specification into cardiac and skeletal muscle lineages in gastruloids

“…However, our gastruloid model also presents some limitations. In contrast to gastruloids from human induced pluripotent stem cells, which have been shown to form a heart-tube like structure 33 or human cardioids which have been shown to form multi-chambers heart like structures 61 , our murine gastruloid model does not show robust heart morphogenesis. We also have not observed cardiac crescent like structures as was previously described 34 .…”

Heart in a dish – choosing the rightin vitromodel

“…An impressive follow-up preprint describes the generation of cardioids for all major embryonic heart compartments, which functionally connected to form multi-chamber cardioids with a shared lumen. The authors successfully used these cardioids to model genetic and teratogen-induced heart defects in vitro ( Schmidt et al, 2022 preprint).…”

Induced pluripotent stem cell-based models: Are we ready for that heart in a dish?

“…A very recent paper showed the generation of cardioids with compartment-specific features recapitulating the main structures such as right and left ventricles, atria, outflow tract, and atrioventricular canal ( Schmidt et al, 2022 ). This human cardioid platform allows the modelling of early specification, morphogenesis, and signal contraction propagation of the human embryonic heart.…”