Enhanced Angiogenic and Cardiomyocyte Differentiation Capacity of Epigenetically Reprogrammed Mouse and Human Endothelial Progenitor Cells Augments Their Efficacy for Ischemic Myocardial Repair (original) (raw)

2012, Circulation Research

Rationale: Although bone marrow endothelial progenitor cell (EPC)-based therapies improve the symptoms in patients with ischemic heart disease, their limited plasticity and decreased function in patients with existing heart disease limit the full benefit of EPC therapy for cardiac regenerative medicine. Objective: We hypothesized that reprogramming mouse or human EPCs, or both, using small molecules targeting key epigenetic repressive marks would lead to a global increase in active gene transcription, induce their cardiomyogenic potential, and enhance their inherent angiogenic potential. Method and Results: Mouse Lin-Sca1 + CD31 + EPCs and human CD34 + cells were treated with inhibitors of DNA methyltransferases (5-Azacytidine), histone deacetylases (valproic acid), and G9a histone dimethyltransferase. A 48-hour treatment led to global increase in active transcriptome, including the reactivation of pluripotency-associated and cardiomyocyte-specific mRNA expression, whereas endotheli...