For the first time, scientists managed to grow a human mini-heart in culture. In the organoid, all the main types of heart cells have formed, as well as structures similar to the coronary vessels and chambers of the heart. Small hearts were regularly beating, and organelles in structure, development and expression of genes were similar to the real hearts of the human embryo. The protocol for creating such hearts is simple and reproducible, the scientists write in a preprint on the bioRxiv portal.
Cardiovascular disease is the leading cause of death in the world, and about one per cent of children are born with congenital heart disease. The study of these diseases is difficult due to the limited choice of model objects: work is carried out mainly on animal organs or cell cultures, which differ in physiological, anatomical and biochemical characteristics 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 organelles are created. In recent decades, biologists have learned to grow a variety of cell lines and whole heart tissues from stem cells, but so far no one has been able to simulate the development of entire organelles in a culture that would be anatomically and histologically close to the human heart.
Scientists from the United States, led by Aitor Aguirre of Michigan State University, have developed a protocol for growing heart organelles. Human pluripotent stem cells were centrifuged so that they coalesced into spherical structures, and then grown alternately in media with different concentrations of activator and inhibitor of the Wnt signalling pathway.
By the 15th day of cultivation, a two-layer spherical organoid was formed: outside the epicardial cell, inside - cardiomyocytes. On the sixth day, the cell ball began to contract, and by the tenth day, the beating became regular. The organoid was penetrated by 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 heart chambers. The formation of blood vessels and chambers was enhanced when two morphogens were added to the medium: BMP4 and activin A.
RNA sequencing of the organoid at different times confirmed that the stages of its development are the same as in the heart of a human embryo. In the organoid, genes were expressed that provide the main functions of the heart: conduction, contractility, calcium metabolism. Scientists have also found all major types of heart cells in the organoid, including epicardial, endothelial, endocardial, and fibroblast cells. This histological diversity and genetic similarity to a real heart have not been achieved in single-layer cell cultures.
In conclusion, the authors of the work emphasized that the protocol they invented is simple (fairly common equipment for growing cell lines) and reproducible. The resulting cardiac organoid is similar in the variety of cells and morphological organization to the heart of a human embryo, which means that it can be used to study both the normal development of the heart and its deviations.
Photos: Yonatan Israeli et al. / bioRxiv, 2020