KDR receptor: A key marker defining hematopoietic stem cells

Studies on pluripotent hematopoietic stem cells (HSCs) have been hindered b y 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 CD3 4(+)KDR(+) cell fraction. Conversely, Lineage-committed HPCs were in the CD 34(+)KDR(-) subset. On the basis of Limiting dilution analysis, the HSC fre quency 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 cor d 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 perc ent, for the cell subfraction resistant to growth factor starvation. Thus, KDR is a positive functional marker defining stem cells and distinguishing them from progenitors.