Atrial-like Engineered Heart Tissue: An In Vitro Model of the Human Atrium

Abstract

Summary: Cardiomyocytes (CMs) generated from human induced pluripotent stem cells (hiPSCs) are under investigation for their suitability as human models in preclinical drug development. Antiarrhythmic drug development focuses on atrial biology for the treatment of atrial fibrillation. Here we used recent retinoic acid-based protocols to generate atrial CMs from hiPSCs and establish right atrial engineered heart tissue (RA-EHT) as a 3D model of human atrium. EHT from standard protocol-derived hiPSC-CMs (Ctrl-EHT) and intact human muscle strips served as comparators. RA-EHT exhibited higher mRNA and protein concentrations of atrial-selective markers, faster contraction kinetics, lower force generation, shorter action potential duration, and higher repolarization fraction than Ctrl-EHTs. In addition, RA-EHTs but not Ctrl-EHTs responded to pharmacological manipulation of atrial-selective potassium currents. RA- and Ctrl-EHTs’ behavior reflected differences between human atrial and ventricular muscle preparations. Taken together, RA-EHT is a model of human atrium that may be useful in preclinical drug screening. : Lemme et al. developed a human, atrial-like engineered heart tissue from hiPSCs that could be used as an in vitro model of the human atrium to evaluate selectivity of novel ion channel blockers for atrial fibrillation. Keywords: hiPSC-CMs, pluripotent stem cells, atrial differentiation, atrial myocytes, atrial-like cells, retinoic acid, engineered heart tissue, cardiac tissue engineering, atrial fibrillation