AUTHOR=Pioner Josè Manuel , Fornaro Alessandra , Coppini Raffaele , Ceschia Nicole , Sacconi Leonardo , Donati Maria Alice , Favilli Silvia , Poggesi Corrado , Olivotto Iacopo , Ferrantini Cecilia
TITLE=Advances in Stem Cell Modeling of Dystrophin-Associated Disease: Implications for the Wider World of Dilated Cardiomyopathy
JOURNAL=Frontiers in Physiology
VOLUME=11
YEAR=2020
URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.00368
DOI=10.3389/fphys.2020.00368
ISSN=1664-042X
ABSTRACT=
Familial dilated cardiomyopathy (DCM) is mostly caused by mutations in genes encoding cytoskeletal and sarcomeric proteins. In the pediatric population, DCM is the predominant type of primitive myocardial disease. A severe form of DCM is associated with mutations in the DMD gene encoding dystrophin, which are the cause of Duchenne Muscular Dystrophy (DMD). DMD-associated cardiomyopathy is still poorly understood and orphan of a specific therapy. In the last 5 years, a rise of interest in disease models using human induced pluripotent stem cells (hiPSCs) has led to more than 50 original studies on DCM models. In this review paper, we provide a comprehensive overview on the advances in DMD cardiomyopathy disease modeling and highlight the most remarkable findings obtained from cardiomyocytes differentiated from hiPSCs of DMD patients. We will also describe how hiPSCs based studies have contributed to the identification of specific myocardial disease mechanisms that may be relevant in the pathogenesis of DCM, representing novel potential therapeutic targets.