Surgical injury induces the mobilization of endothelial progenitor cells

Abstract

Background Endothelial progenitor cells (EPCs) are derived from the bone marrow and incorporate into the foci of tumor neovascularization to increase tumor growth. We hypothesized that surgery induces the mobilization of EPCs. Methods C57BL/6 mice were assigned randomly to standardized laparotomy or anesthesia-only treatment groups (n = 102 mice). Animals were killed at 6, 24, 48, and 72 hours. Bone marrow EPCs were detected by blood flow cytometric dual staining for stem cell antigen-1/cKit. Circulating EPCs were characterized in blood by vascular endothelial growth factor receptor 2 +/macrophage activating complement-1 − staining. EPCs were detected in splenic homogenates by dual staining for lectin and acetylated low-density lipoprotein uptake. Plasma vascular endothelial growth factor was determined by enzyme-linked immunosorbent assay. Results Surgery induced increases in bone marrow and splenic EPC levels (0.2% ± 0.01% vs 2.9% ± 0.3%) at 24 hours and in circulating EPC levels (2.5% ± 0.01% vs 35.2% ± 6%) at 48 hours compared with control subjects (P < .001). Surgical injury also caused an increase in vascular endothelial growth factor release (81 ± 8 vs 14 ± 2 pg; P > .02). Conclusions EPCs were mobilized by surgical injury, which may have implications for residual and metastatic tumor growth during the perioperative period.