Angiogenesis-mediated neovascularization correlates with recovery after intracerebral implantation of neural stem cells (NSCs) in stroke. To elucidate NSCs' mechanism of action, it is essential to understand how these interact with the brain's vasculature after implantation. Using an all-human endothelial cell (EC, D3 cell line) and NSC (STROC05 and CTXOE03) co-culture model, fluorescently activated cell sorting (FACS) was used to isolate each cell type for a comparison of gene expression between monocultures of undifferentiated proliferating and differentiated non-proliferating cells. Gene expression for angiogenic factors (vascular endothelial growth factor, platelet derived growth factor, angiopoietin), as well as cell survival (brain derived neurotrophic factor, fibroblast growth factor) and migration (stromal cell-derived factor-1a) were measured and contrasted with the corresponding receptors on each cell type. The cellular source of extracellular matrix defining the basement membrane (vitronectin, fibronectin, laminin, collagen I and IV) and neuropil (hyaluronic acid, aggrecan, neurocan, thrombospondin, nidogen and brain associated link protein-1) was evaluated for NSCs and ECs. Co-culturing dramatically changed the expression profiles of each cell type in comparison to undifferentiated, but also differentiated cells. These results indicate that monocultures provide a poor model to investigate the cellular signaling involved in a tissue repair response. Co-cultures of NSCs and ECs forming vasculature-like structures (VLS) provide a more complex model to investigate NSC-induced neovascularization. These in vitro studies are essential to tease out individual cell signaling in NSCs and ECs to develop a mechanistic understanding of the efficacy of NSCs as a therapeutic for stroke.

中文翻译：

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模拟神经血管微环境的人类神经干细胞和内皮细胞中基因表达变化的表征。

血管生成介导的新血管形成与脑内植入神经干细胞 (NSC) 后脑卒中的恢复相关。为了阐明 NSCs 的作用机制，必须了解这些神经干细胞在植入后如何与大脑的脉管系统相互作用。使用全人内皮细胞（EC、D3 细胞系）和 NSC（STROC05 和 CTXOE03）共培养模型，荧光激活细胞分选 (FACS) 用于分离每种细胞类型，以比较未分化的单培养之间的基因表达。增殖和分化的非增殖细胞。血管生成因子（血管内皮生长因子、血小板衍生生长因子、血管生成素）以及细胞存活（脑衍生神经营养因子、成纤维细胞生长因子）和迁移（基质细胞衍生因子-1a）被测量并与每种细胞类型上的相应受体进行对比。对定义基底膜（玻连蛋白、纤连蛋白、层粘连蛋白、I 型和 IV 型胶原蛋白）和神经纤维（透明质酸、蛋白聚糖、神经聚糖、血小板反应蛋白、nidogen 和脑相关链接蛋白-1）的细胞外基质的细胞来源进行 NSC 和 EC 评估。与未分化细胞和分化细胞相比，共培养显着改变了每种细胞类型的表达谱。这些结果表明，单一培养提供了一个较差的模型来研究参与组织修复反应的细胞信号传导。NSCs 和 ECs 的共培养形成血管样结构 (VLS)，提供了一个更复杂的模型来研究 NSC 诱导的新血管形成。