Chen Tong, Bai Hao, Shao Ying, Arzigian Melanie, Janzen Viktor, Attar Eyal, Xie Yi, Scadden David T, Wang Zack Z
Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Stem Cells. 2007 Feb;25(2):392-401. doi: 10.1634/stemcells.2006-0145. Epub 2006 Oct 12.
The molecular mechanisms that regulate human blood vessel formation during early development are largely unknown. Here we used human ESCs (hESCs) as an in vitro model to explore early human vasculogenesis. We demonstrated that stromal cell-derived factor-1 (SDF-1) and CXCR4 were expressed concurrently with hESC-derived embryonic endothelial differentiation. Human ESC-derived embryonic endothelial cells underwent dose-dependent chemotaxis to SDF-1, which enhanced vascular network formation in Matrigel. Blocking of CXCR4 signaling abolished capillary-like structures induced by SDF-1. Inhibition of the SDF-1/CXCR4 signaling pathway by AMD3100, a CXCR4 antagonist, disrupted the endothelial sprouting outgrowth from human embryoid bodies, suggesting that the SDF-1/CXCR4 axis plays a critical role in regulating initial vessel formation, and may function as a morphogen during human embryonic vascular development.
在早期发育过程中调节人类血管形成的分子机制在很大程度上尚不清楚。在这里，我们使用人类胚胎干细胞（hESCs）作为体外模型来探索早期人类血管生成。我们证明，基质细胞衍生因子-1（SDF-1）和CXCR4与hESC衍生的胚胎内皮分化同时表达。hESC衍生的胚胎内皮细胞对SDF-1进行剂量依赖性趋化，这增强了基质胶中血管网络的形成。阻断CXCR4信号消除了SDF-1诱导的毛细血管样结构。CXCR4拮抗剂AMD3100对SDF-1/CXCR4信号通路的抑制破坏了人类胚状体的内皮芽生，表明SDF-1/CXCR4轴在调节初始血管形成中起关键作用，并且可能在人类胚胎血管发育过程中作为一种形态发生素发挥作用。
