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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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Submitted April 6, 2005
Accepted June 4, 2005
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*
Division of Transplantation Surgery, Karolinska Institutet, Karolinska University Hospital-Huddinge, Stockholm, Sweden
Division of Clinical Immunology, Karolinska Institutet, Karolinska University Hospital-Huddinge, Stockholm, Sweden
* Corresponding author; email: suchitra.holgersson{at}cfss.ki.se.
The monocyte population in blood is considered as a possible source of endothelial precursors. Since endothelial-specific receptor tyrosine kinases act as regulators of endothelial cell functions, we investigated whether the 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 VEGFR-2 (CD14+/VEGFR-2+) were isolated and their phenotypic, morphological and functional capacity was compared with monocytes negative for this marker (CD14+/VEGFR-2-). CD14+/VEGFR-2+ cells constituted approximately 2.0±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 the expression of the green fluorescence protein (GFP). Transplantation of GFP-transduced cells into balloon-injured femoral arteries of nude mice significantly contributed to efficient re-endothelialization. CD14+/VEGFR-2- did not exhibit any of the above characteristics. These data demonstrate that expression of VEGFR-2 on peripheral blood monocytes is essential for their endothelial-like functional capacity, and supports the notion of a common precursor for monocytic and endothelial cell lineage. Our results help in clarifying which specific subpopulations may restore damaged endothelium and participate in the maintenance of vascular homeostasis.

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