Israeli researchers simulate arrhythmia on first-ever 3D vascular heart

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Israeli researchers have developed 3D engineered heart tissues engineered to simulate the most common type of irregular heartbeat (arrhythmia) – atrial fibrillation – allowing detailed drug research to take place. The tissues, grown from stem cells, pave the way for personalized medications and even implants for cardiac patients in the future.The team at the Technion – Israel Institute of Technology, the Rambam Healthcare Campus (Rambam Medical Center), and colleagues at the McEwen Stem Cell Institute at the University Health Network in Toronto, Canada, successfully produced atrial and ventricular heart tissue derived from human stem cells. Both types of tissue had unique properties in terms of gene and protein expression patterns, electrical activity, and contractile properties, simulating the corresponding tissues found in live hearts.“Separation between these two types of tissues is important because drugs that can improve the function of atrial cells and thus prevent arrhythmias in the auricle are liable to cause harm to ventricular cell function and even induce ventricular arrhythmias,” explained lead researcher Professor Lior Gepstein of the Technion-Israel institute of Technology.“For example, for atrial fibrillation – the most common type of irregular heartbeat that is also responsible for more than a quarter of all strokes – we want to influence the electrical activity of the atrial cells using drugs, without affecting the function of the ventricular tissue. Now that we can individually manufacture the cells of the atrium and the ventricle, we can test each drug for each cell type separately.”The technology has the potential to form the basis for a range of personalized medicines, as it produces tissues based on the patient’s own DNA. To cultivate the tissue, adult cells such as skin or blood would be taken from the patient and regressed to an embryonic stem cell state. The resulting cells are then cultivated in the lab to grow into the tissue required, in this case atrial or ventricular heart tissue.Both the tissues and the methods used to study them could revolutionize the field of drug development as tissue could be grown from the patient’s own stem cells and used to test different treatments in advance of delivering the treatment to the patient. This would allow doctors to identify which therapeutic best meets the need of their patient, improving outcomes.In the longer term, Prof. Gepstein hopes the technology will be used to create tissue for transplants, avoiding the problem of rejection that occurs when foreign tissues to the patient are used. “These tissues will be well received because they are based on the genetic characteristics of the patient him/herself,” he said.The research, published in Nature Communications, complemented a previous study Prof. Gepstein’s lab, using a 2D model of cardiac tissue to study a genetic disorder called the short QT syndrome, which causes arrhythmias and can lead to sudden death. This study demonstrated the potential for using genetic editing (CRISPR) technology to correct the mutation causing short QT syndrome, providing proof-of-concept evidence for this technology’s potential to treat genetic disorders in the future. The research also compliments that done by a team at Tel Aviv University, who last April revealed that they had 3D printed a whole heart including cells, blood vessels, chambers and ventricles, using human source tissues. 



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