In test vessels designed by the Viennese biologist Sasha Mendjan, miniature hearts of a few millimeters in size (also called cardiac organoids) grow from human stem cells, which have both a left and a right pumping chamber and an atrium. In the near future it will be used to develop new drugs.
These miniature hearts develop as real hearts during embryo formation and begin to beat rhythmically. Such ‘multichamber cardioids’ enable biologists and physicians to investigate developmental disorders and diseases of the vital blood pump. They were presented in the trade magazine “Cell”.
Sasha Mendjan from the Institute for Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences (ÖAW) and colleagues produced organoids for the left and right ventricles and atrium from human cells in the laboratory.
When they grew the organoids for the different chambers together, common ‘multichambered heart organoids’ emerged, which the researchers also call ‘multichamber cardioids’. “In it, an electrical signal spread from the atrium to the left ventricle and then to the right ventricle,” says Mendjan.
This is exactly what happens during early heart development in the fetus of any animal (including humans). “We have observed this fundamental process for the first time in a human heart model with all its chambers,” says Mendjan.
Complicated dance of leading and following
Until now, it was not known how the human heart starts beating, the researchers explain. This has now been observed in the multichambered cardioid: “We saw that the ventricles undergo a complex dance of leading and following over the course of their development,” they report: “First, the left ventricle accompanies the developing right ventricle in rhythm.” Two days later, the atrium develops and the heart chambers follow this rhythm.
Multichamber cardioids can be manufactured in large numbers, so that hundreds of miniature heart models of approximately one millimeter can be examined side by side for defects caused by gene changes (mutations) or the effects of substances that cause malformations (teratogens). “The size can be controlled,” Mendjan explains. “We already have organoids that are three to five millimeters in size.”
Respond to disruptions like true hearts
The miniature heart models respond to disturbances just like real hearts. For example, “Talidomide” and “retinoid derivatives” are used in humans to treat blood cancer (leukemia), psoriasis, and acne, but they are known to cause serious heart defects in fetuses. “Both teratogens caused similar, severe chamber-specific defects in the cardiac organoids,” the researchers said. Furthermore, mutations in the model hearts lead to chamber-specific defects that are also observed in human development.
There are no models for good treatments
“In the future, multichambered cardiac organoids could therefore be used for toxicological studies and for the development of new drugs with cardiac chamber-specific effects,” Mendjan explains. There is no effective drug treatment for many heart diseases because there are no models to test active ingredients.
Organoids developed from stem cells from patients with cardiac developmental disorders may also shed light on the cause of the problems and how to treat and prevent them. Producing organs for patient transplants is still science fiction, Mendjan told the APA.
Cardiovascular disease is the most common cause of death worldwide, the researchers explain, with 18 million people worldwide dying from heart disease every year.
Source: Krone
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