Hydrolyzed 5-Azacytidine Enhances Differentiation of Rat Mesenchymal Stem Cells into Cardiomyocytes

The demethylation agent 5-azacytidine (5-aza) is often used to induce the cardiomyogenic differentiation of mesenchymal stem cells (MSCs). Due to the poor stability of 5-aza, it hydrolyzes into two intermediate products, N-(formylamidino)-N′-β-D-ribofuranosylurea and 1-β-D-ribofuranosyl-3-guanylurea within days in a physiological environment. However, the effects of these intermediate products on the differentiation of MSCs into cardiomyocytes have not been investigated. The aim of this study was to elucidate the effects these hydrolysis products on the differentiation of MSCs into cardiomyocytes. The preliminary results reveal that MSCs treated with hydrolyzed 5-aza exhibited a higher differentiation ratio of MSCs into cardiomyocytes, as evidenced by cardiac marker expressions (assessed by gene expression assay, immunofluorescence staining, and flow cytometry assays) after short incubation compared to that for untreated MSCs. These results suggest that the efficiency of the cardiomyogenic differentiation of MSCs can be enhanced by treating the cells with hydrolyzed 5-aza.