Abstract
Recent advancement of human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) technologies has opened the door to next-generation modeling of human cardiac biology and disease. Not only does this alleviate the need for human primary tissue and compensate for the well documented deficiencies of rodent models for cardiovascular disease, but these technologies may lead to the identification of better candidates for clinical development. Unfortunately, most current 2D hiPSC-CM models lack the biochemical, mechanical, and electrical feedback that cardiomyocytes endure in a multi-cellular aligned tissue, which limits their translatability into clinical settings. To address this, we incorporated hiPSC-CMs modeling various genetic dilated cardiomyopathies (DCM) into 3D engineered heart tissues (EHTs). Here, we show these models develop distinguishable contractile defects recapitulating hallmarks of DCM when compared to biologically relevant controls. Moreover, this distinct phenotype is quantitative, reproducible, and demonstrates utility for drug discovery. As this innovative technology continues to develop, EHTs are on the forefront of emerging biomimetic assays that can be used to prevent drug attrition in the late stages of drug development.
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