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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2438-2445.
Prepublished online as a Blood First Edition Paper on May 30, 2006; DOI 10.1182/blood-2006-04-013755.
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STEM CELLS IN HEMATOLOGY
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
From the Divisions of Oncology and Rheumatology, Washington University School of Medicine, St Louis, MO.
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.
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