Department of Biomedical Technologies, Ege University, Izmir, Turkey; Ege University Central Research Test and Analysis Laboratories Research and Application Center (EGE-MATAL), Izmir, Turkey.
Department of Bioengineering, Ege University, Izmir, Turkey.
Int J Biol Macromol. 2019 Apr 1;126:1002-1013. doi: 10.1016/j.ijbiomac.2018.12.257. Epub 2018 Dec 28.
There are several blood-brain barrier (BBB) models available for pharmaceutical research, but none of those are able to properly imitate the permeability of this special barrier. In this study, it is aimed to produce different BBB models with different cellular combinations and different basement membrane polymers, such as polyethylene terephthalate (PET) and bacterial cellulose (BC), which has not been used for BBB models before, to compare their barrier properties. Primary human brain microvascular endothelial cells were seeded on the luminal side and primary human astrocytes and/or primary human brain microvascular pericytes were seeded on the abluminal side of the membranes. Immunofluorescence (IF) staining results indicate that the expression of tight and adherence junction proteins increases on the 5th day of the cultivation. In accordance with Live-Dead staining results, IF images show that cells in the model lose their viability before the 10th day. Transendothelial electrical resistance (TEER) measurements indicate that BC membrane leads to statistically higher (p < 0.05) TEER values than the standard Transwell PET insert membrane. Sucrose and caffeine permeability values of all models are close to in vivo values. BC shows potential to be used as a more reliable basement membrane for BBB models for pharmaceutical research.
有几种血脑屏障 (BBB) 模型可用于药物研究,但没有一种能够正确模拟这种特殊屏障的通透性。在这项研究中,旨在使用不同的细胞组合和不同的基底膜聚合物(如聚对苯二甲酸乙二醇酯 (PET) 和细菌纤维素 (BC))来生产不同的 BBB 模型,BC 以前从未用于 BBB 模型,以比较它们的屏障特性。将原代人脑微血管内皮细胞接种在膜的腔侧,将原代人脑星形胶质细胞和/或原代人脑微血管周细胞接种在膜的基底膜侧。免疫荧光 (IF) 染色结果表明,培养第 5 天,紧密连接和黏附连接蛋白的表达增加。根据 Live-Dead 染色结果,IF 图像显示模型中的细胞在第 10 天之前失去活力。跨内皮电阻 (TEER) 测量表明,BC 膜导致 TEER 值比标准 Transwell PET 插入膜统计学上更高 (p < 0.05)。所有模型的蔗糖和咖啡因通透性值都接近体内值。BC 具有成为更可靠的用于药物研究的 BBB 模型基底膜的潜力。