Cell cultures are instrumental for studying basic and applied aspects of gene and molecular therapy relevant to the treatment of cystic fibrosis (CF). Specifically, human airway epithelial cell cultures maintained at an air-liquid interface and displaying mucociliary differentiation similar to the in vivo epithelium faithfully reproduce the high resistance to gene therapy vectors characteristic of the native human mucosa. These cultures are an excellent model to better understand vector interaction with target cells and provide a strong platform for pre-clinical basic science studies to address issues crucial to the success of gene and molecular therapy for CF. A Tissue Procurement and Cell Culture Core was established at the University of North Carolina (UNC) in 1984, under the auspices of the CF Foundation, to provide standardized cell cultures to CF researchers. The Core has supported UNC Gene Therapy for CF projects since 1993 and has increased its output and capabilities to meet growing research demands. The Core routinely makes available cells and media that are unavailable and/or prohibitively expensive if purchased from commercial suppliers. The historical focus of the Core has been to provide human airway epithelial cell cultures to UNC CF Center investigators. The purpose of the present application is to increase the range of services to the University-wide gene and molecular therapy community by providing human airway epithelial cells in environments more representative of in vivo conditions as well as supplying additional cell types. To accomplish these goals, we propose the following specific aims. 1) To provide well differentiated, normal and CF, large and small airway epithelial cells in novel model systems reproducing important elements of the in vivo airway environment. 2) To provide newly developed, well-differentiated mouse airway epithelial cell cultures suitable for mechanistic studies. 3) To cost effectively provide human pulmonary artery and lung microvascular endothelial cells and hepatocytes, high priority targets for gene therapy. Through these functions, and in conjunction with the other Cores in this application, the Cell Culture Models Core will foster collaborations directed at improving vector efficiency to both the airway epithelium and additional cell and organ systems relevant to the research mission of NIDDK.
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