Abstract 17079: In Vitro Modeling of Duchenne Muscular Dystrophy (DMD) Cardiomyopathy Using Human Induced Pluripotent Stem Cells (hiPSC)

Introduction: Duchenne Muscular Dystrophy (DMD) is the most common and debilitating X-linked muscular dystrophy characterized by absence of dystrophin. A significant cardiomyopathic phenotype is seen in DMD and has emerged as a leading cause of death in DMD. There is limited knowledge of pathophysiology of DMD cardiomyopathy due to the limited availability of patient tissues and no human cardiomyocyte model of DMD exists. We hypothesized the pathophysiology of DMD cardiomyopathy can be modeled by utilizing DMD hiPSC CM and interrogating them at the cellular and molecular level. Methods: Dermal fibroblasts were obtained from patients with DMD cardiomyopathy (dystrophin deletion of exon 4-43) and normal healthy controls. The fibroblasts were reprogrammed to hiPSC using retroviral vectors containing the human transcription factors, OCT4, SOX2, KLF4 and C-MYC. The DMD and control hiPSC lines were differentiated to CM using a directed differentiation protocol. Molecular and physiologic assays were performed at...