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The Influence of Hyaluronic Acid and Glioblastoma Cell Coculture on the Formation of Endothelial Cell Networks in Gelatin Hydrogels
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2017-09-22 , DOI: 10.1002/adhm.201700687
Mai T Ngo 1 , Brendan A Harley 2
Affiliation  

Glioblastoma (GBM) is the most common and deadly form of brain cancer. Interactions between GBM cells and vasculature in vivo contribute to poor clinical outcomes, with GBM‐induced vessel co‐option, regression, and subsequent angiogenesis strongly influencing GBM invasion. Here, elements of the GBM perivascular niche are incorporated into a methacrylamide‐functionalized gelatin hydrogel as a means to examine GBM–vessel interactions. The complexity of 3D endothelial cell networks formed from human umbilical vein endothelial cells and normal human lung fibroblasts as a function of hydrogel properties and vascular endothelial growth factor (VEGF) presentation is presented. While overall length and branching of the endothelial cell networks decrease with increasing hydrogel stiffness and incorporation of brain‐mimetic hyaluronic acid, it can be separately altered by changing the vascular cell seeding density. It is shown that covalent incorporation of VEGF supports network formation as robustly as continuously available soluble VEGF. The impact of U87‐MG GBM cells on the endothelial cell networks is subsequently investigated. GBM cells localize in proximity to the endothelial cell networks and hasten network regression in vitro. Together, this in vitro platform recapitulates the close association between GBM cells and vessel structures as well as elements of vessel co‐option and regression preceding angiogenesis in vivo.

中文翻译:


透明质酸与胶质母细胞瘤细胞共培养对明胶水凝胶内皮细胞网络形成的影响



胶质母细胞瘤(GBM)是最常见和最致命的脑癌。 GBM细胞和体内脉管系统之间的相互作用导致不良的临床结果,GBM诱导的血管选择、退化和随后的血管生成强烈影响GBM侵袭。在这里,GBM 血管周围生态位的元素被纳入甲基丙烯酰胺功能化明胶水凝胶中,作为检查 GBM-血管相互作用的手段。介绍了由人脐静脉内皮细胞和正常人肺成纤维细胞形成的 3D 内皮细胞网络的复杂性,作为水凝胶特性和血管内皮生长因子 (VEGF) 呈现的函数。虽然内皮细胞网络的总长度和分支随着水凝胶硬度的增加和仿脑透明质酸的掺入而减少,但可以通过改变血管细胞接种密度来单独改变。结果表明,VEGF 的共价掺入支持网络形成,与连续可用的可溶性 VEGF 一样强大。随后研究了 U87-MG GBM 细胞对内皮细胞网络的影响。 GBM 细胞定位于内皮细胞网络附近,并在体外加速网络退化。总之,这个体外平台概括了 GBM 细胞和血管结构之间的密切关联,以及体内血管生成之前的血管选择和回归的元素。
更新日期:2017-09-22
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