Alveolar epithelial cells primary models

Primary Alveolar Epithelial Cell Culture Models... 

Steimer A, Franke H, Haltner-Ukomado E, Laue M, Ehrhardt C, Lehr CM (2007) Monolayers of porcine alveolar epithelial cells in primary culture as an in vitro model for drug absorption studies. Eur J Pharm Biopharm [Epub ahead of print] doi 10.1016/j.ejpb.2006.11.006... 

The primary cell culture model is a more valid model for the study of absorption and transport processes of a drug via the pulmonary route. It provides a tight epithelial barrier with morphological and functional properties resembling those of the in-vivo condition. Primary alveolar epithelial cells from rats [39], rabbits [40] and humans [41] which display morphological and biochemical characteristics similar to the native epithelium have been isolated and can be used for drug transport studies. 

Cell culture models to evaluate the pulmonary fate of inhaled drugs have not been used extensively for characterizing inhalation drugs. However, this technique is promising and will be briefly discussed. This section focuses on airway and alveolar epithelial models using cell lines and primary cell culture methods. 

We used in vitro models of lung epithelial cell lines or primary cells to determine E25 permeability. Two different cell types were used to mimic the airway and alveolar epithelium of the lung to study transport. Calu-3, a human cell line derived from an airway carcinoma, when grown at an air/liquid interface, differentiate to form a secretory airway epithelium (17). Rat primary epithelial cells isolated as described by Cheek et al. (18) form a tight barrier similar in structure and function to the alveolar surface. Both cell types when grown to confluence form tight junctions and differentiate and polarize so that the apical or air surface has different characteristics than the basolateral or blood side. The typical transepithelial resistance observed was 350 or >1000 ohms-cm for Calu-3 cells or primary rat alveolar cells, respectively. Once an acceptable resistance was achieved, E25 (2 mg/mL) was placed in either the apical or the basolateral chamber. Cell monolayers were incubated at 37°C for up to 3 hours and ELISA measured the amount of E25 that translocated the epithelial layer and appeared in the receiver well. The apparent permeability (Papp) of the epithelium for E25 was calculated as ... 

---