In vitro models of the human blood–brain barrier (BBB) are increasingly used to develop therapeutics that can cross the BBB for treating diseases of the central nervous system. Here we report a meta-analysis of the make-up and properties of transwell and microfluidic models of the healthy BBB and of BBBs in glioblastoma, Alzheimer’s disease, Parkinson’s disease and inflammatory diseases. We found that the type of model, the culture method (static or dynamic), the cell types and cell ratios, and the biomaterials employed as extracellular matrix are all crucial to recapitulate the low permeability and high expression of tight-junction proteins of the BBB, and to obtain high trans-endothelial electrical resistance. Specifically, for models of the healthy BBB, the inclusion of endothelial cells and pericytes as well as physiological shear stresses (~10–20 dyne cm^–2) are necessary, and when astrocytes are added, astrocytes or pericytes should outnumber endothelial cells. We expect this meta-analysis to facilitate the design of increasingly physiological models of the BBB.

人类血脑屏障 (BBB) 的体外模型越来越多地用于开发能够穿过 BBB 来治疗中枢神经系统疾病的疗法。在此，我们报告了对健康 BBB 以及胶质母细胞瘤、阿尔茨海默病、帕金森病和炎症性疾病中 BBB 的 Transwell 和微流体模型的组成和特性的荟萃分析。我们发现模型类型、培养方法（静态或动态）、细胞类型和细胞比例以及用作细胞外基质的生物材料对于重现血脑屏障紧密连接蛋白的低渗透性和高表达都至关重要，并获得高跨内皮电阻。具体来说，对于健康 BBB 模型，需要包含内皮细胞和周细胞以及生理剪切应力（~10-20 达因 cm ^–2 ），并且当添加星形胶质细胞时，星形胶质细胞或周细胞的数量应超过内皮细胞。我们期望这种荟萃分析能够促进 BBB 越来越多的生理模型的设计。