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Tissue engineering models on the basis of human cardiac cells for the study of cardiac tachyarrhythmia.

Name
Konstantin
Surname
Agladze
Scientific organization
MFTI
Academic degree
Candidate of Physico-mathematical Sciences
Position
Professor
Scientific discipline
Life Sciences & Medicine
Topic
Tissue engineering models on the basis of human cardiac cells for the study of cardiac tachyarrhythmia.
Abstract
In the present study, we report on the development of tissue-engineering model that is based on human cardiomyocytes derived from cell reprogramming. It demonstrates the effectiveness of these models in assessing and determining the efficiency of antiarrhythmics cardiac pharmaceuticals. A patient-specific cardiac tissue models to explore mechanisms of deadly reentry - arrhythmias in patients with prolonged electrocardiographic QT interval is developed.
Keywords
tissue engineering, cardiomyocyte, cell reprogramming, excitation waves, cardiac arrhythmia, optical mapping
Summary

In recent years, tissue-engineering model based on the cardiac cells have shown to be effective in an experimental study of the mechanisms of cardiac arrhythmias, replacing the traditional electrophysiological preparations. These advantages include the good reproducibility and the ability to control tissue architecture via the substrate topography or the architecture of the cultivation polymer matrices. Particularly functional, these models make use of a so-called optical mapping (using fluorescent dyes, marking excited heart cells) for visualization and registration of waves of excitation, controlling myocardial contraction.

With the aid of cultured cardiac tissue it was possible, for example, answer questions such as why certain patterns of conductive heart tissue are arrhythmogenic, how a so-called overdrive pacing can normalize cardiac rhythm, what is the mechanism of the drug suppression of a reentry source while decreasing the excitability of the myocardium, and others.

However, conventional tissue engineering myocardium models have a serious drawback due to the fact that they are based on animal (usually rat) cells. In this case, the set of ion currents through a rat cell membrane is significantly different from human. For example, in rats fast rectifying potassium current, Ikr practically is absent. This fact makes it unsuitable for a rat model any study of Class III antiarrhythmic drugs, which has been used successfully in medical practice and based on blocking Ikr. In the present study, we report on the development of tissue-engineering model that is based on human cardiomyocytes derived from cell reprogramming. The development of patient-specific cardiac tissue models to explore mechanisms of deadly reentry - arrhythmias in patients with the prolonged QT interval, recorded on the electrocardiogram, is also reported.