Each year, about 18 million people die of cardiovascular disease, is the world’s largest killer. Congenital heart disease is the most common birth defect in children. The main bottleneck in the current development of regenerative therapies and the exploration of heart malformations is the lack of human heart physiological models. In the past decade, the field of organoid culture has greatly promoted the speed of biomedical research, such as intestinal tissue, lung tissue, brain, eyes, islets, liver, and skin tissue organoid culture.
The heart is the last organ that lacks this model of tissue self-assembly and the most difficult to overcome [1-2].
Although the method of tissue engineering has been successfully constructed artificial heart tissue [3-4]. The use of human or mouse pluripotent stem cells for 3D culture has produced a miniature spherical model containing cardiomyocytes and other cardiac constituent cells [4-7]. These technologies are conducive to drug screening and other research. However, there is still a lack of self-assembled heart culture models.
On July 6, 2020, the Sasha Mendjan team from the Institute of Molecular Biotechnology of the Austrian Academy of Sciences published an article entitled Cardioidsreveal self-organizing principles of human cardiogenesis on bioRxiv. This article reports on a new self-organizing “cardioids” with in vivo-like architecture.
The study used human pluripotent stem cells to cultivate a self-assembled cardiac organoid containing a heart cavity. The authors found that heart organoid self-assembly is controlled by multiple signals. WNT-BMP signaling mediates chamber formation through the transcription factor HAND1. WNT-VEGF signal regulates endothelial cell morphology and myocardial cavity morphology.
New heart organoid culture process
This study is the first report that heart-shaped heart organoids can be cultured in a Petri dish, and does not require the addition of extracellular matrix for culture. The self-assembled heart organoid culture can achieve endothelial layer, external epicardial layer and myocardial layer structure formation (endothelial, epicardial, myocardial morphogenesis), forming a structure similar to the heart cavity.
Cardiac organ culture imaging
The successful cultivation of self-assembled heart organoids provides an excellent platform for the study of congenital heart disease and opens up new avenues for drug discovery and regenerative medicine.