Culture models of the blood-brain barrier (BBB) are important research tools. Their role in the preclinical phase of drug development to estimate the permeability for potential neuropharmaceuticals is especially relevant. Since species differences in BBB transport systems exist, primate models are considered as predictive for drug transport to brain in humans. Based on our previous expertise we have developed and characterized a non-human primate co-culture BBB model using primary cultures of monkey brain endothelial cells, rat brain pericytes, and rat astrocytes. Monkey brain endothelial cells in the presence of both pericytes and astrocytes (EPA model) expressed enhanced barrier properties and increased levels of tight junction proteins occludin, claudin-5, and ZO-1. Co-culture conditions also elevated the expression of key BBB influx and efflux transporters, including glucose transporter-1, MFSD2A, ABCB1, and ABCG2. The correlation between the endothelial permeability coefficients of 10 well known drugs was higher (R² = 0.8788) when the monkey and rat BBB culture models were compared than when the monkey culture model was compared to mouse in vivo data (R² = 0.6619), hinting at transporter differences. The applicability of the new non-human primate model in drug discovery has been proven in several studies.

中文翻译：

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从原代脑内皮细胞、周细胞和星形胶质细胞制备的灵长类血脑屏障共培养模型的表征

血脑屏障 (BBB) 的培养模型是重要的研究工具。它们在药物开发的临床前阶段评估潜在神经药物渗透性的作用尤其重要。由于 BBB 转运系统存在物种差异，灵长类动物模型被认为可以预测药物向人类大脑的转运。基于我们之前的专业知识，我们使用猴脑内皮细胞、大鼠脑周细胞和大鼠星形胶质细胞的原代培养物开发并表征了非人类灵长类动物共培养 BBB 模型。在周细胞和星形胶质细胞（EPA 模型）存在的情况下，猴脑内皮细胞表现出增强的屏障特性和增加的紧密连接蛋白 occludin、claudin-5 和 ZO-1 的水平。共培养条件还提高了关键 BBB 流入和流出转运蛋白的表达，包括葡萄糖转运蛋白 1、MFSD2A、ABCB1 和 ABCG2。10种知名药物的内皮通透系数之间的相关性较高（R² = 0.8788) 当猴子和大鼠 BBB 培养模型进行比较时，猴子培养模型与小鼠体内数据进行比较时 (R ² = 0.6619)，暗示了转运蛋白的差异。新的非人类灵长类动物模型在药物发现中的适用性已在多项研究中得到证实。