Full-length dystrophin deficiency leads to contractile and calcium transient defects in human engineered heart tissues.

ABSTRACT: Cardiomyopathy is currently the leading cause of death for patients with Duchenne muscular dystrophy (DMD), a severe neuromuscular disorder affecting young boys. Animal models have provided insight into the mechanisms by which dystrophin protein deficiency causes cardiomyopathy, but there remains a need to develop human models of DMD to validate pathogenic mechanisms and identify therapeutic targets. Here, we have developed human engineered heart tissues (EHTs) from CRISPR-edited, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) expressing a truncated dystrophin protein lacking part of the actin-binding domain. The 3D EHT platform enables direct measurement of contractile force, simultaneous monitoring of Ca²⁺ transients, and assessment of myofibril structu

SUBMITTER: Bremner SB 

PROVIDER: S-EPMC9393922 | biostudies-literature | 2022 Jan-Dec

REPOSITORIES: biostudies-literature