Characterization of endothelial progenitor cells mobilization following cutaneous wounding

• Published in: Wound repair and regeneration Vol. 18; no. 4; pp. 383 - 390
• Main Authors: Morris, Lee M., Klanke, Charles A., Lang, Stephanie A., Pokall, Stefan, Maldonado, Arturo R., Vuletin, Jose F., Alaee, Datis, Keswani, Sundeep G., Lim, Foong-Yen, Crombleholme, Timothy M.
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.07.2010
• Subjects: Analysis of Variance; Animals; Chemokine CXCL12 - antagonists & inhibitors; Chemokine CXCL12 - physiology; Disease Models, Animal; Down-Regulation - physiology; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Hemangioblasts - physiology; Heterocyclic Compounds - pharmacology; Mice; Mice, Inbred Strains; Myeloid Progenitor Cells - physiology; Neovascularization, Physiologic - physiology; Receptors, CXCR4 - antagonists & inhibitors; Receptors, CXCR4 - physiology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - physiology; Statistics, Nonparametric; Transcription, Genetic - physiology; Wound Healing - physiology; Wounds, Penetrating - physiopathology
• ISSN: 1067-1927; 1524-475X
• DOI: 10.1111/j.1524-475X.2010.00596.x

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.