Understanding Arrhythmogenic Cardiomyopathy: Advances through the Use of Human Pluripotent Stem Cell Models

Cardiomyopathies (CMPs) represent a significant healthcare burden and are major cause of heart failure leading to premature death. Several CMPs now recognized have strong genetic basis, including arrhythmogenic cardiomyopathy (ACM), which predisposes patients arrhythmic episodes. Variants in one the five genes (PKP2, JUP, DSC2, DSG2, DSP) encoding proteins desmosome known subset ACM, we classify as desmosome-related ACM (dACM). Phenotypically, this disease may lead sudden cardiac death young athletes and, during late stages, is often accompanied by myocardial fibrofatty infiltrates. While pathogenicity has been well established through animal studies limited supplies primary human cells, these systems drawbacks that limit their utility relevance understanding disease. Human induced pluripotent stem cells (hiPSCs) emerged powerful tool for modeling vitro can overcome challenges, they reproducible scalable source cardiomyocytes (CMs) recapitulate patient phenotypes. In review, provide an overview dACM, summarize findings other model linking with disease, up-to-date summary work conducted hiPSC-cardiomyocyte (hiPSC-CM) models dACM. context hiPSC-CM system, highlight novel contributed our enumerate limitations, prospects, directions research consider towards future progress.