Characterization of endothelial progenitor cells mobilization following cutaneous wounding

Authors

  • Lee M. Morris MD,

    1. The Fetal Care Center of Cincinnati, Division of Pediatric General, Thoracic, and Fetal Surgery, Cincinnati Children's Hospital, University of Cincinnati College of Medicine, Cincinnati, Ohio
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  • Charles A. Klanke MS,

    1. The Fetal Care Center of Cincinnati, Division of Pediatric General, Thoracic, and Fetal Surgery, Cincinnati Children's Hospital, University of Cincinnati College of Medicine, Cincinnati, Ohio
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  • Stephanie A. Lang BS,

    1. The Fetal Care Center of Cincinnati, Division of Pediatric General, Thoracic, and Fetal Surgery, Cincinnati Children's Hospital, University of Cincinnati College of Medicine, Cincinnati, Ohio
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  • Stefan Pokall MD,

    1. The Fetal Care Center of Cincinnati, Division of Pediatric General, Thoracic, and Fetal Surgery, Cincinnati Children's Hospital, University of Cincinnati College of Medicine, Cincinnati, Ohio
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  • Arturo R. Maldonado MD,

    1. The Fetal Care Center of Cincinnati, Division of Pediatric General, Thoracic, and Fetal Surgery, Cincinnati Children's Hospital, University of Cincinnati College of Medicine, Cincinnati, Ohio
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  • Jose F. Vuletin MD,

    1. The Fetal Care Center of Cincinnati, Division of Pediatric General, Thoracic, and Fetal Surgery, Cincinnati Children's Hospital, University of Cincinnati College of Medicine, Cincinnati, Ohio
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  • Datis Alaee MS,

    1. The Fetal Care Center of Cincinnati, Division of Pediatric General, Thoracic, and Fetal Surgery, Cincinnati Children's Hospital, University of Cincinnati College of Medicine, Cincinnati, Ohio
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  • Sundeep G. Keswani MD,

    1. The Fetal Care Center of Cincinnati, Division of Pediatric General, Thoracic, and Fetal Surgery, Cincinnati Children's Hospital, University of Cincinnati College of Medicine, Cincinnati, Ohio
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  • Foong-Yen Lim MD,

    1. The Fetal Care Center of Cincinnati, Division of Pediatric General, Thoracic, and Fetal Surgery, Cincinnati Children's Hospital, University of Cincinnati College of Medicine, Cincinnati, Ohio
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  • Timothy M. Crombleholme MD

    1. The Fetal Care Center of Cincinnati, Division of Pediatric General, Thoracic, and Fetal Surgery, Cincinnati Children's Hospital, University of Cincinnati College of Medicine, Cincinnati, Ohio
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Reprint requests:
Timothy M. Crombleholme, MD, The Fetal Care Center of Cincinnati, Division of Pediatric General, Thoracic and Fetal Surgery, Cincinnati Children's Hospital, University of Cincinnati College of Medicine, 3333 Burnet Avenue, MLC 11025, Cincinnati, OH 45229 3039.
Tel: +1 513 636 6259;
Fax: +1513 636 5959;
Email: timothy.crombleholme@cchmc.org

ABSTRACT

Bone marrow (BM)-derived endothelial progenitor cells (EPCs) are known to play an important role in neovascularization and wound healing. We investigated the temporal effects of cutaneous wounding on EPC surface markers within the peripheral blood and BM, and to better understand the role of the stromal cell-derived factor-1 alpha (SDF-1α/CXCR4) axis on EPC mobilization after wounding. FVB/NJ mice were administered bilateral 8 mm circular full-thickness skin wounds. Peripheral blood and BM were isolated at daily intervals postwounding through day 7 and analyzed for EPC mobilization characteristics and levels of SDF-1α. Cutaneous wounding was found to cause a transient increase in EPC mobilization that peaked on day 3. In contrast, SDF-1α protein within blood plasma was observed to significantly decrease on days 3, 4, and 7 following cutaneous wounding. BM levels of SDF-1α protein decreased to a nadir on day 3, the same day as peak mobilization was observed to occur. The decrease in BM SDF-1α protein levels was also associated with a decrease in SDF-1α mRNA suggesting transcriptional down-regulation as a contributing factor. This study for the first time characterizes EPC mobilization following cutaneous wounding in mice and supports a major role for the SDF-1α/CXCR4 axis in regulating mobilization within the BM, without evidence for systemic increases in SDF-1α.

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