Aging in the Atherosclerosis Milieu May Accelerate the Consumption of Bone Marrow Endothelial Progenitor Cells

OBJECTIVE: We have demonstrated that bone marrow cells from young and wild-type (WT), but not old apoE-/-, mice are capable of preventing atherosclerosis. This study was performed to elucidate the numerical and functional changes underlying the efficacy difference between young and old bone marrow. METHODS AND RESULTS: CD34+/VEGFR2+ conventional endothelial progenitor cells and lin-/cKit+/Sca-1+ hematopoietic stem cells did not differ numerically or functionally between young and old apoE-/- bone marrow. Fluorescence-activated cell sorter analysis, however, showed that a group of cells (simple little cells or SLCs), characteristically located in the lower left quadrant of forward scatter/side scatter flow cytometric plot, were markedly decreased in old WT and apoE-/- marrow, but abundantly present in young WT and apoE-/- bone marrow. The SLC fraction was mainly composed of lin-/cKit-/Sca-1- cells. In vitro differentiation assay demonstrated substantially more efficient endothelial differentiation of lin-/cKit-/Sca-1- SLCs than other bone marrow fractions at a single cell level and en masse. Furthermore, old lin-/cKit-/Sca-1- SLCs had a trend of decreased endothelial differentiation capability. CONCLUSIONS: Lin-/cKit-/Sca-1- SLCs may represent a previously unrecognized cell population, enriched for endothelial progenitors. The identification of these cells may help improve the efficacy of cell therapy.