Stem Cell Research (Nov 2015)

C-kit+ resident cardiac stem cells improve left ventricular fibrosis in pressure overload

  • Andrey Kazakov,
  • Timo Meier,
  • Christian Werner,
  • Rabea Hall,
  • Birgit Klemmer,
  • Christina Körbel,
  • Frank Lammert,
  • Christoph Maack,
  • Michael Böhm,
  • Ulrich Laufs

DOI
https://doi.org/10.1016/j.scr.2015.10.017
Journal volume & issue
Vol. 15, no. 3
pp. 700 – 711

Abstract

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To investigate the effect of resident cardiac stem cells (RCSC) on myocardial remodeling, c-kit+ RCSC were isolated from hearts of C57Bl/6-Tg (ACTb-EGFP)1Osb/J mice expressing green fluorescent protein and expanded in vitro. C57/Bl6N wildtype mice were subjected to transverse aortic constriction (TAC, 360 μm) or sham-operation. 5 × 105 c-kit+ RCSC or c-kit− cardiac cells or cell buffer were infused intravenously 24 h post-surgery (n = 11–24 per group). Hypoxia-inducible factor-1α-mRNA in left ventricles of TAC mice was enhanced 24 h after transplantation. 35 days post-TAC, the density of c-kit+ RCSC in the myocardium was increased by two-fold. Infusion of c-kit+ resident cardiac stem cells post-TAC markedly reduced myocardial fibrosis and the expression of collagen Iα2 and connective tissue growth factor. Infusion of c-kit− cardiac cells did not ameliorate cardiac fibrosis. In parallel, expression of pro-angiogenic mediators (FGFb, IL-4, IL-6, TGFß, leptin) and the density of CD31+ and CD31+ GFP+ endothelial cells were increased. Transplantation reduced brain- and atrial natriuretic peptides and the cardiomyocyte cross-sectional area. Infusion of c-kit+ resident cardiac stem reduced the rate of apoptosis and oxidative stress in cardiomyocytes and in non-cardiomyocyte cells.

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