Human CD34 /KDR Cells Are Generated From Circulating CD34 Cells After Immobilization on Activated Platelets

Objective—The presence of kinase-insert domain-containing receptor (KDR) on circulating CD34 cells is assumed to be indicative for the potential of these cells to support vascular maintenance and repair. However, in bone marrow and in granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood, less than 0.5% of CD34 cells co-express KDR. Therefore, we studied whether CD34 /KDR cells are generated in the peripheral circulation. Methods and Results—Using an ex vivo flow model, we show that activated platelets enable CD34 cells to home to sites of vascular injury and that upon immobilization, KDR is translocated from an endosomal compartment to the cell-surface within 15 minutes. In patients with diabetes mellitus type 2, the percentage of circulating CD34 co-expressing KDR was significantly elevated compared to age-matched controls. When treated with aspirin, the patients showed a 49% reduction in the generation of CD34 /KDR cells, indicating that the level of circulating CD34 /KDR cells also relates to in vivo platelet activation. Conclusion—Circulating CD34 /KDR are not mobilized from bone marrow as a predestined endothelial progenitor cell population but are mostly generated from circulating multipotent CD34 cells at sites of vascular injury. Therefore, the number of circulating CD34 /KDR cells may serve as a marker for vascular injury. (Arterioscler Thromb Vasc Biol. 2011;31:408-415.)