KDR Receptor: A Key Marker Defining Hematopoietic Stem Cells

Abstract

Studies on pluripotent hematopoietic stem cells (HSCs) have been hindered by lack of a positive marker, comparable to the CD34 marker of hematopoietic progenitor cells (HPCs). In human postnatal hematopoietic tissues, 0.1 to 0.5% of CD34(+) cells expressed vascular endothelial growth factor receptor 2 (VEGFR2, also known as KDR). Pluripotent HSCs were restricted to the CD34+KDR+ cell fraction. Conversely, lineage-committed HPCs were in the CD34+KDR- subset. On the basis of limiting dilution analysis, the HSC frequency in the CD34+KDR+ fraction was 20 percent in bone marrow (BM) by mouse xenograft assay and 25 to 42 percent in BM, peripheral blood, and cord blood by 12-week long-term culture (LTC) assay. The latter values rose to 53 to 63 percent in LTC supplemented with VEGF and to greater than 95 percent for the cell subfraction resistant to growth factor starvation. Thus, KDR is a positive functional marker defining stem cells and distinguishing them from progenitors.

Antitumour efficacy of VEGFR2 tyrosine kinase inhibitor correlates with expression of VEGF and its receptor VEGFR2 in tumour models

“…The VEGFR2 protein expression in tumour xenografts was analysed by flow cytometry using single-cell suspensions from freshly harvested tumour tissue (Ziegler et al, 1999). The FACS data for four or five different tumour samples for each xenograft was collected in four-decade mode, gated for single cells, analysed to calculate the mean channel difference (M d ), which represents the magnitude of difference between VEGFR2-specific staining and nonspecific isotype staining.…”

Roles of two VEGF receptors, Flt-1 and KDR, in the signal transduction of VEGF effects in human vascular endothelial cells

“…Flk-1 knockout mice, which die by embryonic day 8.5 (E8.5), lack both ECs and hematopoietic cells (Shalaby et al, 1995). Indeed, KDR is shown to be a key marker de®ning hematopoietic stem cells in human postnatal hematopoietic tissue (Ziegler et al, 1999). In contrast, Flt-1 knockout mice, which also die around E8.5, have abundant ECs, which do not assemble in functional vessels (Fong et al, 1995).…”

Defective proliferative capacity and accelerated telomeric loss of hematopoietic progenitor cells in rheumatoid arthritis

“…Circulating BM-derived stem cells represent a small population of nucleated blood cells (15). Within the CD34ϩ population of circulating HSCs, a subpopulation expresses the vascular endothelial growth factor receptor 2 (VEGFR-2) and likely represents endothelial precursor cells that give rise to new blood vessels (16,17). VEGFR-2ϩ CD34ϩ cells have been localized in synovial tissue from RA as well as osteoarthritis patients (18), and a decreased number of endothelial precursor cells has been found in RA patients (19), suggesting that circulating progenitor cells accumulate in and feed the inflammatory lesions.…”