内皮祖细胞在胶质瘤新生血管中的募集和整合作用

Incorporation and recruitment of endothelial progenitor cells from human umbilical cord blood in glioma neovascularization

目的探讨内皮祖细胞(EPCs)在胶质瘤血管新生化过程中的作用。方法采用密度梯度离心法分离人脐血EPCs。应用人脑胶质瘤细胞系U87细胞建立原位移植动物模型,于瘤细胞接种后第7天将EPCs经尾静脉注入荷瘤鼠,并分别于尾静脉注射后7、14、21d观察EPCs植入后在移植瘤血管新生过程中的募集、整合作用以及对肿瘤生长的影响。结果胶质瘤原位移植模型成瘤率为100%。在EPCs植入后14、21d被募集和整合到肿瘤血管中的EPCs数量显著多于第7天(P<0.05),肿瘤微血管密度和移植瘤体积也显著高于对照组(P<0.05)。结论人脐血EPCs能够被募集并整合到肿瘤血管中促进胶质瘤生长,提示其在胶质瘤血管新生化过程中可能具有重要作用。

Objective To investigate the effects of endothelial progenitor cells （EPCs） derived from human umbilical cord blood on glioma neovascularization in vivo. Methods EPCs were isolated from human umbilical cord blood by density gradient centrifugation. U87 glioblastoma cells were implanted into the brain of nude mice using a stereotactic technique for replicating an orthotopieally implanted human glioblastoma model. On day 7 after U87 cell implantation,EPCs were injected into tumor-bearing mice via their vena caudalis. Incorporation and recruitment of endothelial progenitor cells in neovascularization of malignant glioma in vivo were examined respectively by confocal laser scanning microscopy on day 7,14,21 after EPCs transplantation,and the expansion of the tumor mass were observed. Results Gliomas were formed in all the injected nude mice. The number of EPCs incorporated and recruited into newly formed tumor vessels on day 14,21 after EPCs transplantation were significantly exceeded that at day 7 （P〈0. 05）. Moreover,the volume and vascular density of U87 xenotransplant were significantly increased in EPCs group than those in con trol group （P〈0.05）. Conclusion EPCs derived from human umbilical cord blood may be recruited and incorporated into the growing brain tumor neovasculature,and promote tumor growth, which suggests that EPCs may play an important role in glioma neovascularization.