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C-kit+ CD45− cells found in the adult human heart represent a population of endothelial progenitor cells

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Abstract

Although numerous reports support the existence of stem cells in the adult heart, few studies have been conducted using human cardiac tissue. Therefore, cells from human cardiac atrial biopsies were analyzed regarding progenitor properties. Expression of stem cell markers was analyzed using fluorescence-activated cell sorting. This identified a small population of C-kit+ cells, which could be further subdivided based on expression of CD45. The C-kit+ CD45+ population was determined to be of mast cell identity, while the C-kit+ CD45− population expressed mRNA of the endothelial lineage. Since the number of cells obtainable from biopsies was limited, a comparison between directly isolated and monolayer and explant cultured cells, respectively, was carried out. While both cultures retained a small population of mast cells, only monolayer culture produced a stable and relatively high percentage of C-kit+ CD45− cells. This population was found to co-express endothelial progenitor cell markers such as CD31, CD34, CXCR4, and FLK-1. The mRNA expression profile was similar to the one from directly isolated cells. When sorted cells were cultured in endothelial differentiation medium, the C-kit+ CD45− population retained its expression of endothelial markers to a large extent, but downregulated progenitor markers, indicating further differentiation into endothelial cells. We have confirmed that the human cardiac atrium contains a small C-kit+ CD45− population expressing markers commonly found on endothelial progenitor cells. The existence of an endothelial progenitor population within the heart might have future implications for developing methods of inducing neovascularization after myocardial infarction.

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Acknowledgments

We thank Marion Walser for excellent technical assistance, Linda Thimour-Bergström and Christine Roman-Emanuel for skilful handling of the biopsies, and all members of the heart research team for valuable discussions. This work was supported by grants from the Swedish Heart-Lung Foundation, AstraZeneca, the Inga-Britt and Arne Lundberg Research Foundation, the Swedish Research Council grant no. 2005-75444 and ALF/LUA Research Grant from the Sahlgrenska University Hospital.

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  1. Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, The Sahlgrenska Academy, Gothenburg University, 413 45, Göteborg, Sweden

    Joakim Sandstedt, Marianne Jonsson, Anders Lindahl & Julia Asp

  2. Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Göteborg, Sweden

    Anders Jeppsson

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  1. Joakim Sandstedt
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Sandstedt, J., Jonsson, M., Lindahl, A. et al. C-kit+ CD45− cells found in the adult human heart represent a population of endothelial progenitor cells. Basic Res Cardiol 105, 545–556 (2010). https://doi.org/10.1007/s00395-010-0088-1

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