Increase of ABCG2/BCRP+ side population stem cells in myocardium after ventricular unloading

Abstract

A significant decrease in mean cardiomyocyte DNA content and increased numbers of diploid cardiomyocytes after unloading has been demonstrated, suggesting a numerical increase of cardiomyocytes. Despite a thorough search in that study, no mitoses explaining a potential net increase of cardiomyocytes has been observed. The heart harbors several stem cell populations, including c-kit (CD117)(+) stem cells and side population cells (SPC), which may proliferate after unloading and thus contribute to the generation of diploid cardiomyocytes. In this study we sought to determine, whether there is an increase of ABCG2(+) SPC and CD117(+) stem cells after unloading. In paired myocardial samples (prior to and after LVAD), the number of cells with immunoexpression of ABCG2, c-kit/CD117 and MEF-2 was assessed by immunohistochemistry. Their number was morphometrically determined and these data were correlated with the mean cardiomyocyte DNA content. A significant increase of SPC and cells with coexpression of c-kit and MEF-2 after unloading was observed from 0.00013% in CHF to 0.0011%, and 0.013% to 0.035%, respectively after unloading (p = 0.001). A significant positive correlation between both SPC and cells with coexpression of c-kit and MEF-2 expression was observed (p = 0.007 and 0.01). No correlation was found between the number of SPC and the mean cardiomyocyte DNA content. SPC are increased significantly in the myocardium after ventricular unloading, suggesting a role for stem cell proliferation during "reverse cardiac remodeling." These cells might proliferate and commit to different cell lineages, such as cardiomyocytes or endothelium, and thus ameliorate cardiac function.