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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:113.)
© 2007 American Heart Association, Inc.

Vascular Biology

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

Shoukang Zhu; Xialin Liu; Ying Li; Pascal J. Goldschmidt-Clermont; Chunming Dong

From the Division of Cardiology (S.Z., X.L., P.J.G.-C., C.D.), Department of Medicine, Duke University Medical Center, Durham, NC; and Shanghai East Hospital (Y.L.), Tongji University, Shanghai, China. Current address for P.J.G.-C.: Miller School of Medicine, University of Miami, Fla.

Correspondence to Chunming Dong, Division of Cardiology, Department of Medicine, Duke University Medical Center, Box 3444, Durham, NC 27710. E-mail chunming.dong{at}duke.edu

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.

A group of cells (simple little cells or SLCs) were markedly decreased in the marrow of old wild-type and apoE^–/– mice, relative to their young counterparts. Lineage negative cKit-/Sca-1- cells, the predominant cell type in the SLC population, displayed efficient conversion to a mature endothelial phenotype in vitro.

Key Words: endothelial progenitor cells • vascular repair • bone marrow • aging • atherosclerosis

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