Purpose

This study aimed to characterize a commercially available primary human nasal epithelial cell culture and its gene expression of a wide range of drug transporters under different culture conditions.

Methods

Human nasal cells were cultured in three different types of culture media at the air-liquid (A-L) or liquid-liquid (L-L) interfaces for 1 or 3 wks. The effects of the different cell culture conditions were evaluated using light and electron microscopy, transepithelial electrical resistance (TEER) measurements, permeation studies with dextran, and gene expression profiling of 84 drug transporters.

Results

The type of culture medium affected cell ultrastructure, TEER, and dextran permeation across epithelia. The expression of 20 drug transporter genes depended on the culture interface and/or time in culture; the A-L interface and longer time in culture favored higher expression levels of five ABC and seven SLC transporters.

Conclusions

Culture conditions influence the morphology, barrier formation, permeation properties, and drug transporter expression of human nasal epithelial cells, and this must be taken into consideration during the establishment and validation of in vitro models. A thorough characterization of a nasal epithelial model and its permeability properties is necessary to obtain an appropriate standardized model for the design of aerosol therapeutics and drug transport studies.

中文翻译：

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不同的培养条件会影响药物转运蛋白的基因表达，超微结构和原代人鼻上皮细胞的通透性。

目的

这项研究旨在表征市售的人鼻上皮细胞培养物及其在不同培养条件下多种药物转运蛋白的基因表达。

方法

将人鼻细胞在三种不同类型的培养基中在气-液（AL）或液-液（LL）界面培养1或3周。使用光学和电子显微镜，跨上皮电阻（TEER）测量，右旋糖酐的渗透研究以及84种药物转运蛋白的基因表达谱，评估了不同细胞培养条件的影响。

结果

培养基的类型影响整个上皮细胞的超微结构，TEER和右旋糖酐渗透。20种药物转运蛋白基因的表达取决于培养界面和/或培养时间。AL接口和较长的培养时间有利于5种ABC和7种SLC转运蛋白的较高表达水平。

结论

培养条件会影响人鼻上皮细胞的形态，屏障形成，渗透特性和药物转运蛋白的表达，在建立和验证体外模型时必须考虑到这一点。鼻上皮模型及其渗透性的全面表征对于获得用于气雾剂治疗和药物转运研究设计的适当标准化模型是必要的。