Generation of Induced pluripotent stem cells from Peripheral Blood Mononuclear Cells of an X-linked Dilated Cardiomyopathy Patient.

Abstract

X-linked dilated cardiomyopathy (XLDCM) is a serious heart condition with high morbidity and mortality caused by splice site mutations in intron 1 of the DMD gene located in the X chromosome[1]. Reduced or absence of the Dystrophin protein encoded by the DMD gene increases the susceptibility of the muscle cells to the mechanical stress and therefore early muscle cell damage, inflammation, necrosis and eventually fibrosis with fatty replacement of both skeletal and cardiac muscles. This leads to muscle weakness and dilated cardiomyopathy[2]. With little effect on the skeletal muscles, the DMD gene mutations lead to the specific absence of Dystrophin expression in cardiomyocytes, resulting in early signs of heart failure and quick deterioration to most XLDCM patients. Currently there is no curative treatment and heart transplantation is often required. It is therefore an important condition for study researching on treatment and development of therapies. The rapid development of regenerative medicine applying induced pluripotent stem cells (iPSCs) and CRISPR/Cas9 genome editing technology sheds light on novel therapeutic strategy for XLDCM[3] We aimed to generate integration-free iPSCs derived from the peripheral blood mononuclear cells (PBMCs) of an XLDCM patient with a c.31+1 G>A mutation in the intron1 splice site of the DMD gene. A healthy donor was recruited as normal control. We will also do precise CRISPR/Cas9 genome editing with the patient’s iPSCs and myogenic lineage differentiation for future translational research purpose.