Delgado-Rivera Roberto, Harris Suzan L, Ahmed Ijaz, Babu Ashwin N, Patel Ripal P, Ayres Virginia, Flowers Dexter, Meiners Sally
Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Matrix Biol. 2009 Apr;28(3):137-47. doi: 10.1016/j.matbio.2009.02.001. Epub 2009 Feb 23.
An electrospun nonwoven matrix of polyamide nanofibers was employed as a new model for the capillary basement membrane at the blood-brain barrier (BBB). The basement membrane separates astrocytes from endothelial cells and is associated with growth factors, such as fibroblast growth factor-2 (FGF-2). FGF-2 is produced by astrocytes and induces specialized functions in endothelial cells, but also has actions on astrocytes. To investigate potential autocrine actions of FGF-2 at the BBB, astrocytes were cultured on unmodified nanofibers or nanofibers covalently modified with FGF-2. The former assumed an in vivo-like stellate morphology that was enhanced in the presence of cross-linked FGF-2. Furthermore, astrocyte monolayers established on unmodified nanofibers were more permissive for neurite outgrowth when cultured with an overlay of neurons than similar monolayers established on standard tissue culture surfaces, while astrocytes cultured on FGF-2-modifed nanofibers were yet more permissive. The observed differences were due in part to progressively increasing amounts of FGF-2 secreted by the astrocytes into the medium; hence FGF-2 increases its own expression in astrocytes to modulate astrocyte-neuron interactions. Soluble FGF-2 was unable to replicate the effects of cross-linked FGF-2. Nanofibers alone up-regulated FGF-2, albeit to a lesser extent than nanofibers covalently modified with FGF-2. These results underscore the importance of both surface topography and growth factor presentation on cellular function. Moreover, these results indicate that FGF-2-modified nanofibrillar scaffolds may demonstrate utility in tissue engineering applications for replacement and regeneration of lost tissue following central nervous system (CNS) injury or disease.
聚酰胺纳米纤维的静电纺丝非织造基质被用作血脑屏障（BBB）处毛细血管基底膜的新模型。基底膜将星形胶质细胞与内皮细胞分隔开，并与成纤维细胞生长因子-2（FGF-2）等生长因子相关。FGF-2由星形胶质细胞产生，可诱导内皮细胞发挥特殊功能，但对星形胶质细胞也有作用。为了研究FGF-2在血脑屏障处的潜在自分泌作用，将星形胶质细胞培养在未修饰的纳米纤维或用FGF-2共价修饰的纳米纤维上。前者呈现出类似体内的星状形态，在交联FGF-2存在时这种形态会增强。此外，与在标准组织培养表面上建立的类似单层相比，在未修饰纳米纤维上建立的星形胶质细胞单层在与神经元覆盖物一起培养时对神经突生长更具通透性，而在FGF-2修饰的纳米纤维上培养的星形胶质细胞则更具通透性。观察到的差异部分归因于星形胶质细胞分泌到培养基中的FGF-2量逐渐增加；因此，FGF-2增加其自身在星形胶质细胞中的表达以调节星形胶质细胞与神经元的相互作用。可溶性FGF-2无法复制交联FGF-2的作用。单独的纳米纤维上调了FGF-2，尽管上调程度低于用FGF-2共价修饰的纳米纤维。这些结果强调了表面形貌和生长因子呈现对细胞功能的重要性。此外，这些结果表明，FGF-2修饰的纳米纤维支架可能在组织工程应用中具有实用性，用于中枢神经系统（CNS）损伤或疾病后受损组织的替代和再生。
