Aging in the atherosclerosis milieu may accelerate the consumption of bone marrow endothelial progenitor cells
Aging in the atherosclerosis milieu may accelerate the consumption of bone marrow endothelial progenitor cells
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DOI：
10.1161/01.atv.0000252035.12881.d0
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发表时间：
2007-01-01
影响因子：
8.7
通讯作者：
Dong, Chunming
中科院分区：
文献类型：
--
作者：
Zhu, Shoukang;Liu, Xialin;Dong, Chunming
目的：我们已经证明年轻和野生型（WT）小鼠的骨髓细胞，而不是老年apoE（-/-）小鼠的骨髓细胞能够预防动脉粥样硬化。方法和结果-CD 34（+）/VEGFR 2（+）常规内皮祖细胞和lin（-）/cKit（+）/Sca-1（+）造血干细胞在年轻和老年apoE（-/-）骨髓之间在数量或功能上没有差异。然而，激活细胞分选仪分析显示，一组细胞（简单小细胞或SLC），特征性地位于前向散射/侧向散射流式细胞术图的左下象限，在老年WT和apoE（-/-）骨髓中显著减少，但在年轻WT和apoE（-/-）骨髓中大量存在。SLC组分主要由lin（-）/cKit（-）/Sca-1（-）细胞组成。体外分化试验表明lin（-）/cKit（-）/Sca-1（-）SLC在单细胞水平和内皮细胞水平上比其他骨髓组分更有效地向内皮细胞分化。结论：Lin（-）/cKit（-）/Sca-1（-）SLC可能是一个以前未被认识到的内皮祖细胞富集的细胞群。这些细胞的鉴定可能有助于提高细胞治疗的疗效。
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. Fluorescenceactivated 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.