Characterization of endothelial progenitor cells mobilization following cutaneous wounding.

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-1alpha/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-1alpha. Cutaneous wounding was found to cause a transient increase in EPC mobilization that peaked on day 3. In contrast, SDF-1alpha protein within blood plasma was observed to significantly decrease on days 3, 4, and 7 following cutaneous wounding. BM levels of SDF-1alpha protein decreased to a nadir on day 3, the same day as peak mobilization was observed to occur. The decrease in BM SDF-1alpha protein levels was also associated with a decrease in SDF-1alpha 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-1alpha/CXCR4 axis in regulating mobilization within the BM, without evidence for systemic increases in SDF-1alpha.