Generation of ring-shaped human iPSC-derived functional heart microtissues in a Möbius strip configuration

Abstract

Although human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been used for disease modeling and drug discovery, clinically relevant three-dimensional (3D) functional myocardial microtissues are lacking. Here, we developed a novel ring-shaped cardiac microtissue comprised of chamber-specific tissues to achieve a geometrically non-orientable ventricular myocardial band, similar to a Möbius loop. The ring-shaped cardiac tissue was constructed of hiPSC-CMs and human cardiac fibroblasts (hCFs) through a facile cellular self-assembly approach. It exhibited basic anatomical structure, positive cardiac troponin T (cTnT) immunostaining, regular calcium transients, and cardiac-like mechanical strength. The cardiac rings can be self-assembled and scaled up into various sizes with outstanding stability, suggesting their potential for precise therapy, pathophysiological investigation, and large-scale drug screening. Graphic abstract: [Figure not available: see fulltext.]