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：

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透明质酸和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）是最常见和致命的脑癌形式。GBM细胞与体内血管系统之间的相互作用导致不良的临床结果，GBM诱导的血管共存选择，消退以及随后的血管生成强烈影响GBM的侵袭。在这里，GBM血管周围位的元素被掺入甲基丙烯酰胺官能化的明胶水凝胶中，作为检查GBM与血管相互作用的一种手段。呈现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，这些复杂性是水凝胶性质和血管内皮生长因子（VEGF）表现的函数。内皮细胞网络的总长度和分支随着水凝胶刚度的增加和模拟脑透明质酸的结合而减少，可以通过改变血管细胞的播种密度来单独改变它。结果表明，与连续可用的可溶性VEGF一样，VEGF的共价掺入也能稳定地支持网络的形成。随后研究了U87-MG GBM细胞对内皮细胞网络的影响。GBM细胞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细胞与血管结构之间的紧密联系，以及体内血管生成之前血管共存和消退的要素。随后研究了U87-MG GBM细胞对内皮细胞网络的影响。GBM细胞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细胞与血管结构之间的紧密联系，以及体内血管生成之前血管共存和消退的要素。随后研究了U87-MG GBM细胞对内皮细胞网络的影响。GBM细胞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细胞与血管结构之间的紧密联系，以及体内血管生成之前血管共存和消退的要素。