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.