Tracheo-Bronchial Epithelial Cell Lines

Calu-3 (American type culture collection ATCC HTB-55) is a human bronchial epithelial cell line derived from an adenocarcinoma of the lung [59], This cell line has been shown to exhibit serous cell properties and form confluent monolayers of mixed cell phenotypes, including ciliated and secretory cell types [60], but the cilia are formed very irregularly and seem to disappear with increasing passage number (unpublished observations, C.E. and B.F.). Calu-3 cells have shown utility as a model to examine transport [61-63] and metabolism in human bronchial epithelial cells for many therapeutic compounds [64], Furthermore, they have been used in a number of particlecell interaction studies [65-67], The interactions between respiratory epithelial cells and particulates are discussed more in detail in Chap. 19. 

A relatively new cell line that has not to date been characterised for its use in biopharmaceutics is based on primary airway epithelial cells infected with retroviruses expressing hTERT and HPV-16 E6/E7 (NuLi-1) [54], NuLi-1 cells were cultured on plastic up to passage 30. When grown on collagen-coated, semi-permeable membranes (Millicell-PCF), NuLi-1 TEER decreased only slightly over the 30 passages from 685 31 to 389 21 ohm.cm2. The TEER of NuLi-1 is similar to that observed with the primary bronchial cultures of 532 147 ohm.cm2. Thus, NuLi-1 cells can form an electrically tight airway epithelial barrier that mimics active and passive ion transport properties of primary human bronchial epithelial cells [54], 

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A variety of cell culture systems for the modelling of the tracheo-bronchial epithelium are available. These include primary cultures and cell lines of human and animal origins, plus airway cells with characteristics of lung disease such as CF. The advantages and limitations of using a simple culture system compared to one that recreates to a greater extent the epithelial structure and function in vitro should be considered according to the pre-clinical application required. However, this choice is complicated by the lack of comparative data, both between the different cell systems and for in vitro-in vivo correlation, upon which to base such decisions. 

While a number of immortalised cell lines emanating from different cell types of the airway (i.e., tracheo-bronchial) epithelium of lungs from various mammalian species are available (see Chap. 10), reliable and continuously growing cell lines that possess AEC morphology and phenotype are not reported to date. Most studies use cell lines of alveolar epithelial origin for drug absorption studies, while the observations are hard or meaningless to extend to in vivo human situation. 

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