Neuhaus Winfried, Lauer Regina, Oelzant Silvester, Fringeli Urs P, Ecker Gerhard F, Noe Christian R
Department of Medicinal Chemistry, University of Vienna, Pharmacy Center, Althanstrasse 14, A-1090 Vienna, Austria.
J Biotechnol. 2006 Aug 20;125(1):127-41. doi: 10.1016/j.jbiotec.2006.02.019. Epub 2006 May 26.
A flow based hollow-fiber in vitro model of the blood-brain barrier (BBB) was established. The immortalised porcine brain microvascular endothelial cell line PBMEC/C1-2 was cultured in a pulsatile hollow-fiber cartridge system (Cellmax Quad). The usability of PBMEC/C1-2 in the flow based hollow-fiber model was increased from three days in the originally used Transwell model up to four months due to the application of shear stress and co-culturing with glioma cell line C6. It was shown that the tightness of PBMEC/C1-2 layers was enhanced significantly in astrocyte conditioned medium (ACM) and in co-culture. The morphology of PBMEC/C1-2 and C6 was visualised by environmental scanning electron microscopy (ESEM). Permeation studies were accomplished with a set of benzodiazepines. The raw data were processed with three different calculation models and the results were compared with permeability coefficients obtained with an established Transwell model. In summary a flow based hollow-fiber BBB in vitro model was developed, which can be used to perform experiments with physiological (e.g., regulation of BBB permeability), pharmacological (e.g., pharmacokinetics and dynamics) and pathophysiological (e.g., effects of diseases on BBB permeability and vice versa) objectives.
建立了一种基于流动的血脑屏障（BBB）中空纤维体外模型。将永生化猪脑微血管内皮细胞系PBMEC/C1-2培养在脉动中空纤维盒系统（Cellmax Quad）中。由于施加了剪切应力并与胶质瘤细胞系C6共培养，PBMEC/C1-2在基于流动的中空纤维模型中的可用性从最初使用的Transwell模型中的三天提高到了四个月。结果表明，在星形胶质细胞条件培养基（ACM）和共培养中，PBMEC/C1-2层的紧密性显著增强。通过环境扫描电子显微镜（ESEM）观察了PBMEC/C1-2和C6的形态。用一组苯二氮䓬类药物进行了渗透研究。对原始数据采用三种不同的计算模型进行处理，并将结果与使用已建立的Transwell模型获得的渗透系数进行比较。总之，开发了一种基于流动的中空纤维血脑屏障体外模型，可用于进行具有生理学（如血脑屏障通透性调节）、药理学（如药代动力学和动力学）和病理生理学（如疾病对血脑屏障通透性的影响及反之亦然）目标的实验。
