Researchers have developed a way to grow human heart tissue that can function as a model for the upper chambers of the heart, known as atria. The network, derived from human pluripotent cells (hiPCSs), beats, expresses genes, and responds to drugs in a manner similar to a real human atrium. The model, explained November 8 in the journal Stem Cell Report, it may be useful to evaluate the mechanism of disease and drugs for atrial fibrillation – the most common type of arrhythmia.
In contrast to standard 2D culture, cardiomyocytes originating stem cells are bred in ways that they form 3D defeating heart tissue resembling the atrial heart muscle. In particular, cells show expression of atrial-like genes, contractile strength, contraction and kinetics of relaxation, electrophysiological properties, and pharmacological responses to atrial-selective drugs. According to the authors, engineered heart tissue can function as a human atrial model for both the mechanistic study of atrial fibrillation and for preclinical drug screening.
"This is the first time that human atrial heart tissue has been produced in vitro from a major source of hiPSC," said first author Marta Lemme of the University of Hamburg-Eppendorf Medical Center. "This can be useful both for academic laboratories and the pharmaceutical industry, because to test potential new drugs, we need to produce an in vitro model of atrial fibrillation. And the first step is to get cells that resemble human atrial cardiomyocytes," said Lemme.
Lemme and senior study author Thomas Eschenhagen of the University of Hamburg-Eppendorf Medical Center set out to achieve this goal by producing atrial-like cardiomyocytes from hiPSCs using a vitamin A metabolite called all-trans retinoic acid. This technique involves genes reprograming blood or skin cells taken from human donors to the embryonic state such as stem cells and then treating these immature cells with all-trans retinoic acid to convert them to atrial-like cardiomyocytes.
"But the novelty of this study is the combination of hipsc differentiation into atrial cardiomyocytes with a 3D environment," said Lemme. "In fact, we show that the 3D environment supports differentiation of the atrial phenotype compared to standard 2D culture. The special value of our study is the direct comparison of our 3D engineering heart tissue with original human atrial tissue obtained from patients on the molecule and functional level."
More than 33 million people worldwide suffer from atrial fibrillation, and the prevalence is increasing. Uncoordinated high-frequency contractions in the atria increase the risk of blood clots, strokes, and heart failure. Unfortunately, existing treatments such as antiarrhythmic drugs have limited efficacy and can cause adverse effects. In addition, the development of new drugs has been hampered by difficulties in isolating and maintaining human atrial cardiomyocytes, or heart muscle cells. Animal models have limited predictive power because they do not accurately represent the physiology of human cardiomyocytes.
"This atrial muscle strip represents a great opportunity to model atrial fibrillation in plates and test drugs," Lemme said. "However, improvements can still be made to achieve greater similarity with human atrial tissue. For us, the next step is to test various ways to induce arrhythmias, study the electrical remodeling mechanism of atrial fibrillation and test new potential drugs."
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