Platelet-derived stromal cell-derived factor-1 regulates adhesion and promotes differentiation of human CD34+ cells to endothelial progenitor cells
Platelet-derived stromal cell-derived factor-1 regulates adhesion and promotes differentiation of human CD34+ cells to endothelial progenitor cells
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DOI：
10.1161/circulationaha.107.714691
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发表时间：
2008-01-15
期刊：
影响因子：
37.8
通讯作者：
Gawaz, Meinrad
中科院分区：
文献类型：
--
作者：
Stellos, Konstantinos;Langer, Harald;Gawaz, Meinrad
背景-病变器官中祖细胞的外周归巢对于组织再生至关重要。趋化因子基质细胞衍生因子-1（SDF-1）调节CD 34（+）干细胞的归巢。我们评估了血小板衍生的SDF-1在粘附和人CD 34（+）细胞分化为内皮祖细胞中的作用。方法和结果粘附的血小板表达大量的SDF-1，并在体外和体内募集CD 34（+）细胞。SDF-1或其反受体CXCR 4的单克隆抗体在体外高动脉剪切下和小鼠颈动脉结扎后抑制粘附血小板上的干细胞粘附，如通过活体荧光显微镜测定的。在流动条件下，粘附于人动脉内皮细胞的血小板可增强CD 34（+）细胞在内皮上的粘附，这一过程可被抗SDF-1抑制。在小鼠肠缺血/再灌注过程中，抗SDF-1和抗CXCR 4，而不是同种型对照抗体，消除了微循环中CD 34（+）细胞的募集。此外，血小板衍生的SDF-1与CXCR 4受体结合促进血小板诱导的CD 34（+）细胞向内皮祖细胞的分化，如体外集落形成试验所证实的。由于组织再生依赖于祖细胞向外周血管系统的募集及其随后的分化，血小板衍生的SDF-1可能有助于血管和心肌再生。
Background-Peripheral homing of progenitor cells in areas of diseased organs is critical for tissue regeneration. The chemokine stromal cell-derived factor-1 (SDF-1) regulates homing of CD34(+) stem cells. We evaluated the role of platelet-derived SDF-1 in adhesion and differentiation of human CD34(+) cells into endothelial progenitor cells.Methods and Results-Adherent platelets express substantial amounts of SDF-1 and recruit CD34(+) cells in vitro and in vivo. A monoclonal antibody to SDF-1 or to its counterreceptor, CXCR4, inhibits stem cell adhesion on adherent platelets under high arterial shear in vitro and after carotid ligation in mice, as determined by intravital fluorescence microscopy. Platelets that adhere to human arterial endothelial cells enhance the adhesion of CD34(+) cells on endothelium under flow conditions, a process that is inhibited by anti-SDF-1. During intestinal ischemia/reperfusion in mice, anti-SDF-1 and anti-CXCR4, but not isotype control antibodies, abolish the recruitment of CD34(+) cells in microcirculation. Moreover, platelet-derived SDF-1 binding to CXCR4 receptor promotes platelet- induced differentiation of CD34(+) cells into endothelial progenitor cells, as verified by colony-forming assays in vitro.Conclusions-These findings imply that platelet-derived SDF-1 regulates adhesion of stem cells in vitro and in vivo and promotes differentiation of CD34(+) cells to endothelial progenitor cells. Because tissue regeneration depends on recruitment of progenitor cells to peripheral vasculature and their subsequent differentiation, platelet-derived SDF-1 may contribute to vascular and myocardial regeneration.