Bronchial mucose produced by tissue engineering:: A new tool to study cellular interactions in asthma

Background: The use of fiberoptic bronchial biopsies has improved our understanding of the immunopathology of asthma. However this approach offers a limited ability to perform mechanistic studies observing cell-cell and cell-matrix interactions, which are a key issue in the study of airway remodeling. Tissue engineering is a technique that combines the use of biology and engineering expertise to generate a limitless amount of tissue from small samples. This technology allows for the study of cell interactions under conditions as close as possible to the natural environment. Objective: The aim of this study was to evaluate the feasibility of an engineered human bronchial mucosa as a model to study cellular interactions in asthma, Methods: Human bronchial fibroblasts from normal and asthmatic donors were incorporated into collagen gel. Bronchial epithelial cells were seeded over this gel and then cultured in an air-liquid interface in the presence or the absence of T lymphocytes, Biopsy specimens from these engineered mucosa were taken for structural and ultrastructural analysis, and T lymphocytes were harvested and used to localize IL-5. Results: Histologic analysis showed that engineered mucosa with normal bronchial cells presented a pseudostratified ciliated epithelium with the presence of mucus secretory cells. The electron microscopy analysis confirmed these histologic results. These features were comparable with those observed in normal bronchial tissues. However, in engineered mucosa from asthmatic subjects, the tissue structure was disorganized, particularly the epithelial cell arrangement. The percentage of IL-5(+) lymphocytes was significantly (P =.03) higher in engineered bronchial mucosa from asthmatic subjects (87% +/- 2%) compared with mucosa from normal volunteers (2% +/- 0.3%). Conclusion: Using tissue engineering, we produced an in vitro model of bronchial mucosa from normal and asthmatic subjects, These models could be a valuable tool to better understand key mechanisms Involved in inflammation and airway repair.