The micro-hearts are shrinking
Biologists have grown small human hearts from stem cells
Alice Bakhareva, N+1
For the first time, scientists managed to grow a working human mini-heart in culture. Small hearts regularly contracted, and organoids were similar in structure, development and gene expression to the real hearts of a human embryo. The protocol for creating such hearts is simple and reproducible, scientists write in a preprint on the bioRxiv portal (Israel et al., Generation of Heart Organoids Modeling Early Human Cardiac Development Under Defined Conditions).
Voids of the organoid, similar to the chambers of the heart (figure from the article in bioRxiv).
You can look at the murky video of the shrinking "heart" in the press release of MSU Scientists Grow The First Functioning Mini Human Heart Model - VM.
Cardiovascular diseases are the main cause of death in the world, and about one percent of children are born with a congenital heart defect. The study of these diseases is difficult due to the limited choice of model objects: the work is carried out mainly on animal organs or cell cultures, which differ in physiological, anatomical and biochemical features from the human heart.
A convenient solution would be to grow whole artificial hearts in vitro from stem cells – this is how, for example, kidney or intestinal organoids are created. In recent decades, biologists have learned to grow various cell lines and whole heart tissues from stem cells, but so far no one has been able to simulate the development of whole organoids in culture that would be anatomically and histologically close to the human heart.
Scientists from the USA led by Aitor Aguirre from The University of Michigan has developed a protocol for growing cardiac organoids. Human pluripotent stem cells were centrifuged so that they stuck together into spherical structures, and then grown alternately in media with different concentrations of activator and inhibitor of the Wnt signaling pathway.
By the 15th day of cultivation, a two–layer spherical organoid was formed: epicardial cells outside, cardiomyocytes inside. Already on the sixth day, the cellular ball began to shrink, and by the tenth the beating became regular. The organoid was permeated with a network of endothelial cells with a lumen, similar to the system of coronary vessels. In addition, several voids have formed in the artificial heart, lined with endothelium and resembling the chambers of the heart. The formation of vessels and chambers was enhanced when two morphogens were added on Wednesday: BMP4 and activin A.
Sequencing of the organoid's RNA at different dates confirmed that the stages of its development are the same as in the heart of a human embryo. The organoid expressed genes that provide the main functions of the heart: conduction, contractility, calcium metabolism. The scientists also found all major types of heart cells in the organoid, including epicardium, endothelium, endocardium and fibroblasts. Such histological diversity and genetic similarity with a real heart could not be achieved in single-layer cell cultures.
In conclusion, the authors of the work emphasized that the protocol they invented is simple (equipment common enough for growing cell lines) and reproducible. The resulting cardiac organoid is similar in cell diversity and morphological organization to the heart of a human embryo, which means that both the normal development of the heart and its abnormalities can be studied on it.
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