Researchers have developed a method of growing human heart tissue known as atria. Tissue derived from human induced pluripotent stem cells (hiPCS) pulses, expresses and responds to drugs in a manner similar to that of real human atrium. This model appeared in the November 8 issue of the journal. Stem cell reportIt can be useful for evaluating disease mechanisms and drugs for atrial fibrillation, the most common type of arrhythmia.
Unlike standard 2D cultures, stem cell-derived myocardial cells were cultured in a manner that formed 3D beating heart tissue similar to atrial heart muscle. Specifically, the cells exhibited atrial-like gene expression, contractility, contraction and relaxation rate, electrophysiological characteristics and pharmacological responses to atrial selective drugs. According to the authors, artificial heart tissue can be used as a human atrium model for both mechanistic studies of atrial fibrillation and preclinical drug screening.
"This is the first time that human atrial cardiac tissue has been produced ex vivo from an unlimited source of hiPSCs," says Marta Lemme, the first author of Harmen-Eppendorf at the University of Hamburg. "In order to test potential new drugs, we need to create a test tube model, the first step is to get cells similar to human atrial myocardial cells," he said. "Says Lemme.
Thomas Eschenhagen of Lemme and senior research author University Medical Center Hamburg-Eppendorf sought to achieve this goal by using a vitamin A metabolite called all-trans retinoic acid to generate atrial-like cardiomyocytes from hiPSCs. This technique is a technique to genetically reprogram blood or skin cells from human donors in a state similar to embryonic stem cells and then convert these immature cells to all-trans retinoic acid to convert them into cardiac myocardial cells.
"But the cliché of this study is the combination of hiPSC differentiation and 3D environment into atrial myocardial cells," Lemme said. "In fact, we have shown that 3D environments prefer to differentiate into atrial phenotypes compared to standard 2D cultures." The special value of our research is that the original human atrial tissue obtained from 3D- Functional level that will be compared ".
More than 33 million people worldwide suffer from atrial fibrillation and are increasing in popularity. Uncontrolled high frequency contractions of the atrium increase the risk of blood clots, stroke and heart attack. Unfortunately, conventional therapies such as antiarrhythmic drugs have limited efficacy and can cause side effects. The development of new drugs also suffers from difficulties in isolating and maintaining human atrial myocardial or cardiac muscle cells. Animal models have limited predictive power because they do not accurately represent the physiology of human myocardial cells.
"This atrial muscle flap is a good opportunity to model atrial fibrillation on plates and test pills," says Lemme. "Nonetheless, improvements can be made so that the similarity to human atrial tissue is much higher. The next step is to investigate the mechanism of electroconversion of atrial fibrillation and to test new potential drugs It is an examination. "
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