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.


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.
Zhu
Shoukang
S
Division of Cardiology, Department of Medicine, Duke University Medical Center, Box 3444, Durham, NC 27710, USA.
Liu
Xialin
X
Li
Ying
Y
Goldschmidt-Clermont
Pascal J
PJ
Dong
Chunming
C
D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology*; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002452:Cell Count; D002454:Cell Differentiation; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D004727:Endothelium / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism
D000950:Antigens, Ly; D001057:Apolipoproteins E; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019009:Proto-Oncogene Proteins c-kit