The Influence of Hyaluronic Acid and Glioblastoma Cell Coculture on the Formation of Endothelial Cell Networks in Gelatin Hydrogels.
The Influence of Hyaluronic Acid and Glioblastoma Cell Coculture on the Formation of Endothelial Cell Networks in Gelatin Hydrogels.
复制标题
透明质酸和胶质母细胞瘤细胞共培养对明胶水凝胶中内皮细胞网络形成的影响。
DOI：
10.1002/adhm.201700687
复制
发表时间：
2017
影响因子：
10
通讯作者：
Harley,BrendanA
中科院分区：
文献类型：
--
作者：
Ngo,MaiT;Harley,BrendanA
胶质母细胞瘤（GBM）是最常见和致命的脑癌形式。体内GBM细胞和血管系统之间的相互作用导致临床结果不佳，GBM诱导的血管共选择、消退和随后的血管生成强烈影响GBM侵袭。在这里，GBM血管周围小生境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-血管相互作用的手段。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性质和血管内皮生长因子（VEGF）呈递的函数。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拟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单独改变。研究表明，VEGF的共价结合与持续可用的可溶性VEGF一样有力地支持网络形成。随后研究了U87-MG GBM细胞对内皮细胞网络的影响。GBM细胞定位于内皮细胞网络附近并加速体外网络退化。总之，该体外平台概括了GBM细胞与血管结构之间的密切关联以及体内血管生成之前的血管共选择和消退要素。
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.