Basic pharmacological research aimed at identifying drugs that may correct the cellular derangements that lead to the debilitating and often fatal lung disease associated with cystic fibrosis requires a continuing and dependable source of cystic fibrosis and """"""""normal"""""""" respiratory tissues. Cell culture techniques that allow the propagation of respiratory epithelial cells and formation of differentiated cell culture model systems provide a necessary and powerful tool for testing candidate drugs. Thus, the primary objective of the Cell Models Core is the collection of CF and non-CF respiratory tract tissues and the preparation of differentiated cultures of the respiratory surface epithelial cells and the tracheobronchial submucosal gland cells. A secondary objective of the Cell Models Core is to identify cell culture conditions that permit full expression of differentiated cellular functions, particularly in cell cultures that have been expanded by serial propagation. A tissue procurement system has been established for obtaining both CF and control nasal and airway tissues. Procured tissue is enzymatically digested, and liberated surface epithelial and submucosal gland acinar cells are established as cell cultures. The surface epithelial cells are studied as primary cell cultures of highly differentiated cell sheets that mimic the structure and function of the native nasal and airway epithelium. To increase the number of cell sheets available for screening compounds, some cell cultures are also expanded by serial propagation. The initial primary cultures of the tracheobronchial gland cells are expanded and then seeded as secondary cultures for experimental use. The conditions in which the passaged gland cells are grown are manipulated to produce cells expressing either a mucous or serous cell phenotype. Having respiratory epithelial cells derived from both the mucosal surface and the submucosal gland cells allows investigators to test candidate drugs for action in the various respiratory tract cells most affected in cystic fibrosis.
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