Bone marrow-derived endothelial progenitor cells do not contribute significantly to new vessels during incisional wound healing

Objective: To assess the contribution of bone marrow (BM)-derived endothelial progenitor cells (EPCs) to the neovascularisation of cutaneous incisional wounds. Methods: Lethally irradiated C57Bl/6 mice were transplanted with BM mononuclear cells from Tie2/lacZ mice, which constitutively overexpressed β-galactosidase (β-gal) in endothelial cells (ECs). Chimeras were wounded and the number of X-gal-stained (β-gal+) BM-derived EPCs were calculated in histological wound sections. Results: EPCs were measured in skin sections from unwounded BM transplant (BMT) mice, or at day 1 and 3 postwounding, at the level of 0.1 ± 0.1 (mean ± SEM) per skin/wound section. In day-5 to day-14 wounds, the number of EPCs increased gradually (1.3 ± 0.5 at day 5 and 4.8 ± 0.9 at day 10), peaking at day 14, when there was a significant increase in the number of EPCs per wound section (6.5 ± 1.7) when compared to unwounded skin. Between days 14 and 18 postwounding, there was a rapid fall-off in the number of β-gal+ EPCs (0.8 ± 0.5 at day 18) and numbers returned to baseline by day 21 (0.1 ± 0.1). No evidence of vascular structures derived from BM-derived EPCs ("in situ" vasculogenesis) was observed and it was calculated that these cells contributed only 4.4% ± 1.5% to total wound ECs at their peak. Conclusion: These findings indicate that the revascularization of dermal incisional wounds primarily occurs through angiogenesis because the low frequency and temporal expression of EPCs suggests that they do not make a significant contribution to the neovascularization process. © 2007 International Society for Experimental Hematology.