Abstract 15368: Zebularine Enhances Cardiomyogenic Differentiation Potential of both Mesenchymal Stem Cells and Mature Fibroblasts
Epigenetic reprogramming ability of demethylating agents during stem cell differentiation has gained enormous interest in the field of regenerative medicine. One of the DNA demethylating agents, zebularine is generally considered a useful promoter of cardiomyogenic differentiation in various stem cell types in vitro. As current therapeutic approaches are limited in preventing ventricular remodeling following myocardial infarction (MI), novel therapeutic approach of transplantation of exogenously differentiated cardiomyocytes could be a better option. We earlier reported the in vitro differentiation potential of zebularine treated rat bone marrow mesenchymal stem cells (MSCs) into cardiac-like cells. In the present study, we investigated whether mature fibroblasts can be differentiated into cardiomyocytes after zebularine treatment. Further, cardiac regeneration and function assessment were performed for both MSCs and fibroblasts. Rat bone marrow MSCs and rat skin fibroblast cell line (CRL1213) were subjected to in vitro treatment of two optimized concentrations (3 and 10 μM) of zebularine. These differentiated or partially differentiated cells were analyzed for the presence of cardiac specific genes, Nkx2.5, cardiac troponin T and GATA4 by RT-PCR and transplanted into rat models of myocardial infarction. Cardiac function was assessed by echocardiography while histological analysis was performed to analyze the reduction in the fibrotic area. We observed increase in the gene expression levels of cardiac specific genes in the treated fibroblasts as was the case with MSCs which suggests that stem cells as well as mature cells have differentiated at least partially to cardiomyocytes. Transplantation of these cardiac-like cells into rat MI model significantly (p<0.05) improved the left ventricular cardiac function in case of both cell types as compared to the control and also decreased fibrosis. It can, therefore, be concluded from the present study that zebularine has the potential to differentiate MSCs as well as mature fibroblasts into cardiac-like cells in vitro which in turn can differntiated into mature cardiomyocytes in vivo.
- Cardiac regeneration
- Myocardial infarction
- Regenerative medicine stem cells
- Ventricular function
Author Disclosures: N. Naeem: None. A. Gul: None. A. Ali: None. I. Khan: None. A. Salim: None.
- © 2014 by American Heart Association, Inc.