Right atrial engineered heart tissue (RA-EHT) exhibited higher atrial-selective markers, faster contraction kinetics, and responded to atrial-selective potassium current manipulation versus Ctrl-EHT.
Right atrial engineered heart tissue derived from hiPSCs provides a functional 3D in vitro model of the human atrium that reflects human atrial muscle behavior, useful for preclinical antiarrhythmic drug screening.
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. (Thu,) conducted a other in Atrial fibrillation. Right atrial engineered heart tissue (RA-EHT) vs. Ctrl-EHT and intact human muscle strips was evaluated on Atrial-selective markers, contraction kinetics, force generation, action potential duration, and repolarization fraction. Right atrial engineered heart tissue (RA-EHT) exhibited higher atrial-selective markers, faster contraction kinetics, and responded to atrial-selective potassium current manipulation versus Ctrl-EHT.