Dai Bingling, Zhang Yanmin, Zhan Yingzhuan, Zhang Dongdong, Wang Nan, He Langchong
1] School of Medicine, Xi'an Jiaotong University, No. 76, Yanta Weststreet, #54, Xi'an, Shaanxi Province 710061, P. R. China [2].
School of Medicine, Xi'an Jiaotong University, No. 76, Yanta Weststreet, #54, Xi'an, Shaanxi Province 710061, P. R. China.
Sci Rep. 2014 Jan 15;4:3693. doi: 10.1038/srep03693.
A novel tissue model for angiogenesis (TMA) is established for effective evaluation of angiogenesis inhibitors or promoters in vitro. Lung tissues were cultured in fibrinogen "sandwich" structure which resembled the formation of neovessels in vivo. The cells and capillary-like structures grew from the lung tissues were identified as endothelial cells and neovessels. Both immunohistochemisty and western blot results indicated that autocrine VEGF bound to the KDR and induced KDR autophosphorylation that could induce the proliferation of endothelial cells and their migration as well as the formation of microvessels on the lung tissue edge. With addition of the TMA, the murine VEGF and cultured medium produced by A549 tumor cells apparently promoted the increase of neovessels. Sorafenib as a tumor angiogenesis inhibitor and Tongxinluo as an angiogenesis promoter were both used to evaluate the TMA performance and they exhibited a good effect on neovessels in the TMA. The model established imitated angiogenesis in vivo and could well serve as an effective method in evaluating the angiogenesis inhibitors or promoters, and could also be practical for screening small molecules that affect blood vessel formation.
建立了一种新型的血管生成组织模型(TMA),用于在体外有效评估血管生成抑制剂或促进剂。将肺组织培养在类似于体内新血管形成的纤维蛋白原“三明治”结构中。从肺组织生长的细胞和毛细血管样结构被鉴定为内皮细胞和新血管。免疫组织化学和蛋白质印迹结果均表明,自分泌的血管内皮生长因子(VEGF)与激酶插入结构域受体(KDR)结合并诱导KDR自身磷酸化,这可诱导内皮细胞增殖及其迁移以及肺组织边缘微血管的形成。加入TMA后,小鼠VEGF和A549肿瘤细胞产生的培养基明显促进了新血管的增加。索拉非尼作为一种肿瘤血管生成抑制剂,通心络作为一种血管生成促进剂,均用于评估TMA的性能,它们对TMA中的新血管均显示出良好的作用。所建立的模型模拟了体内血管生成,可很好地作为评估血管生成抑制剂或促进剂的有效方法,也可用于筛选影响血管形成的小分子。