Human bronchial epithelial cells differentiate to 3D glandular acini on basement membrane matrix.

Wu X, Peters-Hall JR, Bose S, Peña MT, Rose MC
Source: Am J Respir Cell Mol Biol
Publication Date: (2011)
Issue: 44(6): 914-21
Cells used in publication:
Epithelial, bronchial (NHBE), human
Species: human
Tissue Origin: lung
Lonza\\\'s bronchial epithelial cells were used in a 3D model system that investigated hyperplasia and hypertrophy of the respiratory tract submucosal glands. The epithelial cells were differentiated into glandular acini on a basement membrane matrix.
To create a model system that investigates mechanisms resulting in hyperplasia and hypertrophy of respiratory tract submucosal glands, we developed an in vitro three-dimensional (3D) system wherein normal human bronchial epithelial (HBE) cells differentiated into glandular acini when grown on a basement membrane matrix. The differentiation of primary HBE cells into glandular acini was monitored temporally by light microscopy. Apoptosis-induced lumen formation was observed by immunofluorescence analysis. The acinar cells expressed and secreted MUC5B mucin (marker for glandular mucous cells) and lysozyme, lactoferrin, and zinc-a2-glycoprotein (markers for glandular serous cells) at Day 22. ß-Tubulin IV, a marker for ciliated cells, was not detected. Expression of mucous and serous cell markers in HBE glandular acini demonstrated that HBE cells grown on a basement membrane matrix differentiated into acini that exhibit molecular characteristics of respiratory tract glandular acinar cells. Inhibition studies with neutralizing antibodies resulted in a marked decrease in size of the spheroids at Day 7, demonstrating that laminin (a major component of the basement membrane matrix), the cell surface receptor integrin a6, and the cell junction marker E-cadherin have functional roles in HBE acinar morphogenesis. No significant variability was detected in the average size of glandular acini formed by HBE cells from two normal individuals. These results demonstrated that this in vitro model system is reproducible, stable, and potentially useful for studies of glandular differentiation and hyperplasia.