VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells

Abstract

Vascular endothelial growth factor (VEGF) has been shown to promote neovascularization in animal models and, more recently, in human subjects. This feature has been assumed to result exclusively from its direct effects on fully differentiated endothelial cells, i.e. angiogenesis. Given its regulatory role in both angiogenesis and vasculogenesis during fetal development, we investigated the hypothesis that VEGF may modulate endothelial progenitor cell (EPC) kinetics for postnatal neovascularization. Indeed, we observed an increase in circulating EPCs following VEGF administration in vivo. VEGF‐induced mobilization of bone marrow‐derived EPCs resulted in increased differentiated EPCs in vitro and augmented corneal neovascularization in vivo. These findings thus establish a novel role for VEGF in postnatal neovascularization which complements its known impact on angiogenesis.

Endothelial progenitor cells: Implications for cardiovascular disease

“…Stem cells within the bone marrow usually exist in a quiescent state and specific signals stimulate the stem cells to differentiate and to be mobilized into the systemic circulation. Beside humoral factors such as cytokines (51)(52)(53), hormones (51,53,54), chemokines (37,55), and drugs (56-58), exercise training (ET) has been shown to increase the number of circulating EPCs (8,9,59,60).…”

Circulating endothelial progenitor cells and endothelial cells in moyamoya disease

“…As some EPCs are known to contribute to neovascularization by differentiating into mature ECs while other EPC subsets function via paracrine effects, circulating cells have been hypothesized to be involved in vascular remodeling in MMD. They stimulate angiogenic activity of resting endothelial cells leading to their proliferation and sprouting (Asahara et al., 1999). EPCs have been investigated to better understand and characterize MMD pathogenesis, but the results have been conflicting (Jung et al., 2008; Kim et al., 2010; Rafat et al., 2009; Yoshihara et al., 2008).…”

Ex vivo delivered stromal cell-derived factor-1α promotes stem cell homing and induces angiomyogenesis in the infarcted myocardium

“…This provides the required stimulus for mobilization of stem cells from BM niches to the damaged site as a part of a natural repair process [9]. The other key players involved in tissue ischemia-induced mobilization of BM progenitors to the circulation include vascular endothelial growth factor, placenta growth factor, stem cell factor, and granulocyte colony stimulating factor [10][11][12][13]. The effect of intrinsic SDF-1α up-regulated expression is, however, transient and insufficient for cardiac repair [4,6].…”