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Researchers have developed a way to develop human heart tissue that can be used as a model for the upper chambers of the heart, called atria. The tissue, derived from human-induced pluripotent stem cells (hiPCS), beats, expresses genes and responds to drugs in the same way as a real human atrium. The model, described on November 8 in the newspaper Stem Cell Reports, may be useful for evaluating the mechanisms of disease and medications for atrial fibrillation – the most common type of arrhythmia.
Unlike standard 2D culture, cardiomyocytes derived from stem cells have been cultured to form 3D-beating heart tissue resembling atrial heart muscle. Specifically, the cells exhibited atrial-type gene expression, contractile force, contraction and relaxation kinetics, electrophysiological properties, and pharmacological responses to selective atrial drugs. According to the authors, the transformed cardiac tissue could serve as a model for human atrium, both for the mechanistic studies of atrial fibrillation and for the screening of preclinical drugs.
"This is the first time that human atrial heart tissue is generated in vitro from a largely unrestricted source of hiPSC," said first author, Marta Lemme, of the University Medical Center. Hamburg-Eppendorf. "This could be useful for both university labs and the pharmaceutical industry, because to test new potential drugs, we need to generate an in vitro model of atrial fibrillation." And the first step is to get cells that look like to human atrial cardiomyocytes ", Lemme says.
Lemme and the lead author of the study, Thomas Eschenhagen of the Hamburg-Eppendorf University Medical Center, aim to achieve this goal by generating atrial-type cardiomyocytes from hiPSC with the help of of a metabolite of vitamin A called all-trans retinoic acid. This technique consists in genetically reprogramming the blood or skin cells taken from human donors to an embryonic stem-like state, then treating these immature cells with all-trans retinoic acid to convert them into cardiomyocytes of the type atrial.
"But the novelty of this study lies in the combination of hiPSC differentiation in atrial cardiomyocytes with a 3D environment," says Lemme. "In fact, we have shown that the 3D environment promotes differentiation towards an atrial phenotype compared to standard 2D culture.A special value of our study is the direct comparison of our 3D heart tissue with native human atrial tissue. obtained from patients on a functional level. "
More than 33 million people in the world suffer from atrial fibrillation and the prevalence is increasing. Uncoordinated high-frequency contractions of the atria increase the risk of blood clots, stroke, and heart failure. Unfortunately, existing treatments such as antiarrhythmics have limited effectiveness and may have adverse effects. In addition, the development of new drugs has been hindered by the difficulty of isolating and maintaining human atrial cardiomyocytes, or cardiac muscle cells. Animal models have limited predictive power because they do not accurately represent the physiology of human cardiomyocytes.
"These atrial muscle strips are an excellent opportunity to model atrial fibrillation in the dish and test drugs," Lemme said. "Nevertheless, improvements can still be made to achieve even greater similarity with human atrial tissue.For us, the next step is to test various ways to induce arrhythmia, to study remodeling mechanisms." electrical atrial fibrillation and testing for potential new drugs. "
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