13 November 2018

Bioengineered atrium

Artificial heart tissue will help doctors treat arrhythmia

Evgenia Efimova, Vesti

German experts have developed a method for growing human heart tissue. The latter can serve as a model of the atria, the parts of the organ that receive blood from the veins.

Tissue created on the basis of human induced pluripotent stem cells (CHIPSCS) is able to contract and respond to medications, as does a real human atrium.

Today, more than 33 million people worldwide suffer from atrial fibrillation (the most common type of arrhythmia), and this figure is growing.

The danger of this condition is an increase in the risk of blood clots (which is also facilitated by watching TV), strokes and heart failure.

Unfortunately, existing treatments, such as antiarrhythmic drugs, are not as effective as we would like. In addition, the use of some of them leads to side effects.

The creation of new drugs for this disease is hindered by the difficulty of obtaining and maintaining the viability of cardiomyocytes (muscle cells of the heart), which make up the walls of the human atria. And animal models do not sufficiently copy the physiology of human cardiomyocytes.

In this regard, the specialists of the University Clinic Hamburg-Eppendorf decided to create the most reliable model of the atrium.

As reported in the press release For this purpose, they used a technology that includes genetic reprogramming of blood or skin cells taken from donors back into the embryonic state.

Then the scientists treated such "immature" cells with tretinoin (a form of vitamin A) and turned them into atrial cardiomyocytes. As a result, the cells followed the path of development of atrial cardiomyocytes.

Note that induced pluripotent stem cells are an indispensable tool for physicians and biologists. Pluripotency is the ability of such a cell to develop into a cell of any organ and tissue. The word "induced" means that stem cells were forced to become such: they were obtained by "reprogramming" ordinary somatic cells.

The resulting cardiomyocytes were subsequently cultured on a three-dimensional template that repeats the shape of the atria. This form additionally contributed to the fact that the cells became similar to human atrial cells.

"In fact, we have shown that a three–dimensional environment, compared with a two-dimensional culture, promotes differentiation to the atrial phenotype," says the first author of the study, Marta Lemme from the University Clinic Hamburg-Eppendorf.

The authors note that the obtained cardiomyocytes showed contractility, electrophysiological properties and reaction to medications, as well as the real atrium.

"The special value of the study lies in the direct comparison of three–dimensional engineered heart tissue with natural human atrial tissue obtained from patients at the molecular and functional levels," says Lemme.

Experts believe that the designed cardiac tissue will be an excellent model of the human atrium both for studies of the nature of atrial fibrillation and for preclinical screening of drugs.

"For the first time, human atrial tissues were obtained in vitro (in vitro – ed.) from an unlimited source of CHIPSC,– says Lemme.

According to her, the development can be useful to scientific laboratories and the pharmaceutical industry for testing new drugs.

"The [obtained] bands of atrial muscles provide an excellent opportunity to simulate atrial fibrillation in a Petri dish and test drugs," adds Lemme.

Nevertheless, the scientist adds, a lot of work needs to be done to achieve an exact similarity with the real tissue of the human atria.

"The next step will be testing various substances that provoke cardiac arrhythmia, studying the mechanisms of electrical remodeling of atrial fibrillation and testing potential medications," says Lemme about future plans.

The results of the study are presented in the scientific publication Stem Cell Reports (Lemme et al., Atrial-like Engineered Heart Tissue: An In Vitro Model of the Human Atrium).

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