Human Airway Primary Epithelial Cells Show Distinct Architectures on Membrane Supports Under Different Culture Conditions.
Human Airway Primary Epithelial Cells Show Distinct Architectures on Membrane Supports Under Different Culture Conditions.
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DOI：
10.1007/s12013-016-0719-8
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发表时间：
2016-06
影响因子：
2.6
通讯作者：
Shin MC
中科院分区：
文献类型：
--
作者：
Min KA;Rosania GR;Shin MC
为了促进肺给药药物的开发，建立合适的气道上皮细胞模型作为运输屏障来评估药物分子的药代动力学特征是非常必要的。除癌源性细胞系外，正常人支气管上皮细胞（NHBE）作为原代细胞模型，由于其在体内的生理相关性，已被用于药物筛选。因此，为了准确解读不同实验室测得的NHBE药物转运数据，了解不同培养条件下膜上NHBE的生物物理特性非常重要。在本研究中，NHBE在不同培养基的聚酯膜上生长，通过功能分析和共聚焦成像在培养的几天内充分表征了其运输屏障特性和细胞结构。在不同培养基中插入的NHBE细胞分别进行AIC（空气界面培养）和LCC（液体覆盖培养）。AIC条件下的细胞仅在基底外侧培养基上培养，而LCC条件下的细胞在基底外侧培养基上培养。定量显微成像和生物物理检查显示分化的NHBE细胞具有明显的多层结构，表明NHBE是肺靶向药物运输的功能性细胞屏障。
To facilitate drug development for lung delivery, it is highly demanding to establish appropriate airway epithelial cell models as transport barriers to evaluate pharmacokinetic profiles of drug molecules. Besides the cancer-derived cell lines, as the primary cell model, normal human bronchial epithelial (NHBE) cells have been used for drug screenings because of physiological relevance to in vivo. Therefore, to accurately interpret drug transport data in NHBE measured by different laboratories, it is important to know biophysical characteristics of NHBE grown on membranes in different culture conditions. In this study, NHBE was grown on the polyester membrane in different medium and its transport barrier properties as well as cell architectures were fully characterized by functional assays and confocal imaging throughout days of cultures. Moreover, NHBE cells on inserts in different medium were subject to either of AIC (air-interfaced culture) or LCC (liquid-covered culture) condition. Cells in the AIC condition were cultivated on the membrane with medium in the basolateral side only whereas cells with medium in apical and basolateral sides under the LCC condition. Quantitative microscopic imaging with biophysical examination revealed distinct multilayered architectures of differentiated NHBE cells, suggesting NHBE as functional cell barriers for the lung-targeting drug transport.