Engineering micro-alignments of 2- and 3-D hESC-derived ventricular tissues to reproduce anisotropic properties of the native heart: an accurate arrhythmias model for cardiotoxicity screening

Abstract

In the native heart, ventricular CMs are aligned in a highly organized structured manner such that the conduction of electrical signals is anisotropic for directional and coordinated contractions to effectively pump blood. In other words, electrical conduction is asymmetrical (i.e. anisotropy) with distinct transverse and longitudinal velocities. Unlike the native ventricle, clusters of hESC-CMs differentiated using either the EB formation or directed differentiation are random structures with NO obvious organization and anisotropy as we previously published. Using a microgroove technology, here we engineered organized 2- and 3-D hESC-derived ventricular strips, followed by high-resolution optical mapping recordings …