Recent reports indicate that circulating endothelial progenitor cells (EPCs) may be recruited to sites of neovascularization where they differentiate into endothelial cells (EC). As we have previously demonstrated that
adenosine A(2A) agonists promote neovascularization in
wounds, we sought to determine whether
adenosine A(2A) receptor agonist-augmented wound healing involves vessel sprouting (angiogenesis) or
EPC recruitment (vasculogenesis) or both. Four weeks after bone marrow reconstitution from donor FVB/N Tie2GFP transgenic mice, two full-thickness excisional
wounds were performed on the dorsum of FVB/N wild-type mice and treated with either an A(2A) receptor agonist (CGS-21680) or vehicle alone. Vessel density, as measured by CD31 staining, and density of
EPC-derived vessels, as measured by GFP expression, were quantified in a blinded fashion using two-color fluorescence microscopy. We observed nearly a threefold increase in CD31-positive vessels and a more than 10-fold increase in GFP-positive cells in A(2A) agonist-treated 3-day old
wounds, but by 6 days after wounding the differences between A(2A) agonist-treated and vehicle-treated
wounds were no longer statistically significant. In conclusion, this is the first evidence that an exogenous agent such as an
adenosine A(2A) receptor agonist increases neovascularization in the early stages of
wound repair by increasing both
EPC recruitment (vasculogenesis) and local vessel sprouting (angiogenesis).