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Blood, 15 November 2002, Vol. 100, No. 10, pp. 3527-3535
HEMATOPOIESIS
Fibroblast growth factor receptor-1 is expressed by endothelial
progenitor cells
Patricia E. Burger,
Sandra Coetzee,
Wallace L. McKeehan,
Mikio Kan,
Perry Cook,
Yong Fan,
Toshio Suda,
Robert P. Hebbel,
Nicolas Novitzky,
William A. Muller, and
E. Lynette Wilson
From the Departments of Immunology and Hematology,
University of Cape Town, Cape Town, South Africa;
Departments of Cell Biology and Medicine and Kaplan Cancer Center, New
York University Medical Center, New York, NY; Center for Cancer Biology
and Nutrition, Institute for Biosciences and Technology, Texas A & M
University, System Health Science Center, Houston; Zeria Pharmaceutical
Company, Saitama, Japan; Department of Transfusion
Medicine, Columbia University, New York, NY; Department of Cell
Differentiation, Kumamoto University, Kumamoto,
Japan; Department of Medicine, University of Minnesota
Medical School, Minneapolis; Department of Pathology, Weill Medical
College of Cornell University, New York, NY.
Recent experiments show that hematopoietic progenitor cell
populations contain endothelial precursor cells. We have isolated a
population of CD34+ cells that expresses fibroblast growth
factor receptor-1 (FGFR-1) and that differentiates into endothelial
cells in vitro. We find that 4.5% ± 2.1% of CD34+
cells isolated from bone marrow, cord blood, and mobilized peripheral blood express FGFR-1 and that viable CD34+FGFR+
cells are small, with little granularity, and express both primitive hematopoietic and endothelial markers on their surface. The primitive hematopoietic markers AC133, c-kit, and Thy-1 are coexpressed by 75%,
85%, and 64% of CD34+FGFR+ cells,
respectively. Most of the CD34+FGFR+ cells also
express antigens found on endothelial cells, such as CD31, vascular
endothelial growth factor receptor-2, and the endothelial-specific cell
surface marker, vascular endothelial cadherin (VE-cadherin),
whereas 56% to 60% of the cells express Tie, Tek, and the
endothelial-specific marker, P1H12. The
CD34+FGFR+ population is enriched in cells
expressing endothelial-specific antigens compared with the
CD34+ population. Isolated
CD34+FGFR+ cells grow slowly in culture, are
stimulated by fibroblast growth factor-2 and vascular endothelial
growth factor, and give rise to cells that express von Willebrand
factor and VE-cadherin and that incorporate acetylated low-density
lipoprotein. These experiments show that FGFR-1 is expressed by a
subpopulation of CD34+ cells that give rise to endothelial
cells in vitro, indicating that this population contains endothelial
stem/progenitor cells.
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