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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2347-2355.
Prepublished online as a Blood First Edition Paper on June 28, 2005; DOI 10.1182/blood-2005-04-1407.


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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

Only a specific subset of human peripheral-blood monocytes has endothelial-like functional capacity

Elzafir Elsheikh, Mehmet Uzunel, Zhong He, Jan Holgersson, Grzegorz Nowak, and Suchitra Sumitran-Holgersson

From the Divisions of Transplantation Surgery and Clinical Immunology, Karolinska Institutet, Karolinska University Hospital-Huddinge, Stockholm, Sweden.

The monocyte population in blood is considered a possible source of endothelial precursors. Because endothelial-specific receptor tyrosine kinases act as regulators of endothelial cell function, we investigated whether expression of the vascular endothelial growth factor receptor-2 (VEGFR-2) on monocytes is important for their endothelial-like functional capacity. Peripheral-blood monocytes expressing vascular endothelial growth factor receptor-2 (VEGFR-2), or CD14+/VEGFR-2+, were isolated, and their phenotypic, morphologic, and functional capacities were compared with those of monocytes negative for this marker (CD14+/VEGFR-2-). CD14+/VEGFR-2+ cells constituted approximately 2% ± 0.5% of the total population of monocytes and 0.08% ± 0.04% of mononuclear cells in blood. CD14+/VEGFR-2+ cells exhibited the potential to differentiate in vitro into cells with endothelial characteristics. The cells were efficiently transduced by a lentiviral vector driving expression of the green fluorescence protein (GFP). Transplantation of GFP-transduced cells into balloon-injured femoral arteries of nude mice significantly contributed to efficient reendothelialization. CD14+/VEGFR-2- did not exhibit any of these characteristics. These data demonstrate that the expression of VEGFR-2 on peripheral blood monocytes is essential for their endothelial-like functional capacity and support the notion of a common precursor for monocytic and endothelial cell lineage. Our results help clarify which subpopulations may restore damaged endothelium and may participate in the maintenance of vascular homeostasis.


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Circulating endothelial precursors: identification of functional subpopulations
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