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.