G9a histone methyltransferase inhibitor BIX 01294 promotes expansion of adult cardiac progenitor cells without changing their phenotype or differentiation potential

Objectives As a follow‐up to our previous reports showing that the G9a histone methyltransferase‐specific inhibitor BIX 01294 enhances bone marrow cell cardiac potential, this drug was examined for its effects on cardiomyocytes and mouse cardiac progenitor cells ( CPC s). Materials and methods Cardiomyocytes and cardiac explants were cultured ± BIX 01294, and examined for changes in cardiac function, protein and gene expression. Additionally, enriched populations of CPC s, contained in the ‘phase bright cell’ component of explants, were harvested from non‐treated and BIX 01294‐treated cardiac tissue, and assayed for differences in cell phenotype and differentiation potential. Mouse CPC s were cultured with rat cardiomyocytes to allow differentiation of the progenitors to be assayed using species‐specific PCR primers. Results While BIX 01294 had no discernible effect on myocyte function and sarcomeric organization, treatment with this drug significantly increased CPC proliferation, as indicated by enhanced MTT metabolization and BrdUrd incorporation (4.1‐ and 2.0‐fold, respectively, P < 0.001) after 48 h labelling, and increased Ki67 expression (4.8‐fold, P < 0.001) after 7 days culture. Heart explants exposed to BIX 01294 generated 3.6‐fold ( P < 0.005) greater yields of CPC s by 2 weeks culture. Importantly, CPC s obtained from non‐treated and BIX 01294‐treated cultures did not differ in phenotype or differentiation potential. Conclusions These data indicate that BIX 01294 can expand CPC s without undermining their capacity as cardiac progenitors, and suggest that this drug may have utility for generating large numbers of CPC s for cardiac repair.