We show that mouse embryonic endothelial progenitor cells (eEPCs) home preferentially to hypoxic lung metastases when administered intravenously. This specificity is inversely related to the degree of perfusion and vascular density in the metastasis and directly related to local levels of hypoxia and VEGF. Ex vivo expanded eEPCs that were genetically modified with a suicide gene specifically and efficiently eradicated lung metastases with scant patent blood vessels. eEPCs do not express MHC I proteins, are resistant to natural killer cell-mediated cytolysis, and can contribute to tumor vessel formation also in nonsyngeneic mice. These results indicate that eEPCs can be used in an allogeneic setting to treat hypoxic metastases that are known to be resistant to conventional therapeutic regimes.

中文翻译：

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带有自杀基因的胚胎内皮祖细胞在静脉内分娩后靶向低氧性肺转移。

我们显示，静脉内给药时，小鼠胚胎内皮祖细胞（eEPC）优先向低氧性肺转移回家。该特异性与转移中的灌注程度和血管密度成反比，并且与局部缺氧和VEGF水平直接相关。用自杀基因进行了基因修饰的离体扩增eEPCs可以特异性地和有效地根除具有少量专利血管的肺转移。eEPC不表达MHC I蛋白，对天然杀伤细胞介导的细胞溶解具有抗性，并且在非同基因小鼠中也可以促进肿瘤血管的形成。这些结果表明，eEPC可用于同种异体环境中，以治疗已知对常规治疗方案具有抗性的低氧转移灶。