Hurst R D, Fritz I B
Department of Cellular Physiology, The Babraham Institute, Cambridge, United Kingdom.
J Cell Physiol. 1996 Apr;167(1):81-8. doi: 10.1002/(SICI)1097-4652(199604)167:1<81::AID-JCP9>3.0.CO;2-8.
In an effort to obtain a useful in vitro model possessing some of the properties of the blood-brain barrier, we have investigated the properties and interactions of immortalized cell lines. Immortalised human umbilical vein endothelial cells (HUVEC-304), in co-culture with rat C6 glioma cells in a two-chambered assembly, form tight junctional complexes, and develop a permeability barrier having a high transcellular electrical resistance. The endothelial cells generate a barrier with greatest integrity in the presence of glioma cells, or in the presence of glioma cell conditioned medium. Under these conditions, the endothelial cells also display pronounced structural changes which do not occur in the absence of glioma cells. Morphological alterations include a flattening of cell shape from a cuboidal-type to a squamous-type of appearance, and a re-organization of F-actin microfilaments. The integrity of the barrier can be reversibly disrupted by osmotic shock or by tumor necrosis factor-alpha (TNF-alpha). We interpret these observations to indicate that co-cultures of immortalized vascular endothelial and C6 glioma cells provide a model for the investigation of cell-cell interactions required for the generation of a barrier having several properties of the blood-brain barrier.
为了获得一个具有血脑屏障某些特性的有用体外模型,我们研究了永生化细胞系的特性及相互作用。永生化人脐静脉内皮细胞(HUVEC - 304)与大鼠C6胶质瘤细胞在双室装置中共培养时,会形成紧密连接复合物,并形成具有高跨细胞电阻的通透性屏障。在内皮细胞存在胶质瘤细胞或胶质瘤细胞条件培养基的情况下,会形成完整性最高的屏障。在这些条件下,内皮细胞还会表现出明显的结构变化,而在没有胶质瘤细胞时不会出现这种变化。形态学改变包括细胞形状从立方体型扁平为鳞状外观,以及F - 肌动蛋白微丝的重新组织。屏障的完整性可被渗透压休克或肿瘤坏死因子-α(TNF-α)可逆性破坏。我们认为这些观察结果表明,永生化血管内皮细胞与C6胶质瘤细胞的共培养为研究生成具有血脑屏障多种特性的屏障所需的细胞间相互作用提供了一个模型。