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肠道和血脑屏障细胞培养模型的验证及药物渗透比较。

Validation of cell culture models for the intestine and the blood-brain barrier and comparison of drug permeation.

作者信息

Bock Udo, Flötotto Thomas, Haltner Eleonore

机构信息

Across Barriers GmbH, D-Saarbrücken, Germany.

出版信息

ALTEX. 2004;21 Suppl 3:57-64.

PMID:15057409
Abstract

Cell culture models are useful tools to study the uptake of drugs across the barriers of the human body, like the intestine, the skin or the blood-brain barrier. Cell-based in vitro models not only help to reduce the number of animals used but are also much faster to perform, more cost effective and give more reproducible data than animal studies. Given the increasing number of new drugs and chemicals under development, there is an urgent need for the establishment of such in vitro models. However, the validity of such in vitro models is reflected by its ability to accurately predict the behaviour of a substance at the corresponding in vivo barrier. Here, we compare a well-established cell culture model for the intestine, based on Caco-2 colon carcinoma cells, with a primary cell culture model of the blood-brain barrier. We find that Caco-2 cells and cells of the blood-brain barrier have different barrier properties. Therefore, cells used for cell-based assays should be derived from the corresponding tissue to reflect the in vivo barrier characteristics.

摘要

细胞培养模型是研究药物跨人体屏障(如肠道、皮肤或血脑屏障)摄取的有用工具。基于细胞的体外模型不仅有助于减少实验动物的使用数量,而且操作速度更快、成本效益更高,并且比动物研究能提供更具可重复性的数据。鉴于正在研发的新药和化学品数量不断增加,迫切需要建立此类体外模型。然而,此类体外模型的有效性体现在其准确预测物质在相应体内屏障处行为的能力上。在此,我们将一种基于Caco-2结肠癌细胞的成熟肠道细胞培养模型与血脑屏障的原代细胞培养模型进行比较。我们发现Caco-2细胞和血脑屏障细胞具有不同的屏障特性。因此,用于基于细胞的分析的细胞应取自相应组织,以反映体内屏障特征。

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