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1. J Heart Lung Transplant. 2012 Mar;31(3):318-24. Epub 2012 Jan 13.

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

Wohlschlaeger J, Levkau B, Takeda A, Takeda N, Stypmann J, Schmid C, Milting H,
Kurt Werner S, Baba HA.

Department of Pathology and Neuropathology, University Hospital of Essen,
University of Duisburg-Essen, Essen, Germany.

BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.

Copyright © 2012 International Society for Heart and Lung Transplantation.
Published by Elsevier Inc. All rights reserved.

PMID: 22243701 [PubMed - in process]