Submitted April 25, 2006
Accepted May 15, 2006
G-CSF and AMD3100 Mobilize Monocytes into the
Blood that Stimulate Angiogenesis In Vivo Through a
Paracrine Mechanism
Benjamin J. Capoccia, Rebecca M. Shepherd, and Daniel C. Link*
Divisions of Oncology, Washington University School of Medicine
Divisions of Rheumatology, Washington Univerity School of Medicine
* Corresponding author; email: dlink{at}im.wustl.edu.
There is compelling evidence that circulating angiogenic
cells exist that are able to home to sites of vascular
injury and stimulate angiogenesis. However, the number
of angiogenic cells in the blood is low, limiting their
delivery to sites of ischemia. Treatment with certain
cytokines may mobilize angiogenic cells into the blood,
potentially circumventing this limitation. Herein, we
show that treatment with granulocyte colony-stimulating
factor (G-CSF) or AMD3100, a novel CXCR4 antagonist,
significantly stimulated angiogenesis in a murine model
of acute hindlimb ischemia. The kinetics of angiogenic
cell mobilization by these agents appears to be
distinct, with more rapid revascularization observed in
AMD3100 treated mice. Combination treatment with G-CSF
and AMD3100 resulted in the earliest and most complete
recovery in blood flow to the ischemic hindlimb.
Adoptive transfer of mobilized blood mononuclear cells,
while potently stimulating angiogenesis, did not result
in the significant incorporation of donor cells into the
neoendothelium. Cell fractionation studies showed that
it is the monocyte population in the blood that mediates
angiogenesis in this model. Collectively, these data
suggest that monocytes mobilized into the blood by G-CSF
or AMD3100 stimulate angiogenesis at sites of ischemia
through a paracrine mechanism.
