Human airway epithelial cell cultures maintained at an air-liquid interface (ALI) recapitulate mucociliary differentiation found in vivo, regulating ion transport, mucin secetion and ciliated cell beating to reproduce mucociliary clearance mechanisms characterisitic of the native human mucosa. These cultures are an excellent model to study the role of CFTR, ENaC, nucleotide/nucleoside regulatory systems and their integrated function in health and disease as proposed in projects 1-4 of the current PPG, respectively. A Tissue Procurement and Cell Culture Core was established at the University of North Carolina in 1984, under the auspices of the CF Foundation, to provide standardized cell cultures to CF researchers. The Core has supported PPG projects since 2000 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 purpose of the present application is to provide continuity in the supply of airway specimens and large numbers of human airway epithelial cell cultures to PPG investigators, and to support the use of cultures in mechanistic studies. To accomplish these goals, we propose the following specific functions. 1) Tissue Procurement- Obtain nasal and bronchial tissues from normal, disease control, and CF humans as sources of airway epithelial cells and for acute ex vivo experiments, biochemical studies, in situ hybridization and immunohistochemistry. Characterize donors with respect to diagnosis, demographics, and clinical features relevant to research uses. 2) Cell Isolation and Culture- Isolate primary and passaged primary epithelial cells for distribution to project investigators. Maintain stocks of frozen cells and prepare media and substrates to support preparation of well-differentiated airway epithelial cultures as dictated by investigator needs. 3) Genetic Mainipulation of Cell Cultures- Provide support for adenoviral and retroviral expression of molecules under study by project investigators. Through these functions, and in conjunction with other Cores in this application, the Cell Culture Core will support research to better understand mechanisms underlying normal airway surface liquid homeostatsis, which is essential for healthy lungs.
| Schultz, André; Puvvadi, Ramaa; Borisov, Sergey M et al. (2017) Airway surface liquid pH is not acidic in children with cystic fibrosis. Nat Commun 8:1409 |
| Blackmon, R L; Kreda, S M; Sears, P R et al. (2017) Direct monitoring of pulmonary disease treatment biomarkers using plasmonic gold nanorods with diffusion-sensitive OCT. Nanoscale 9:4907-4917 |
| Esther Jr, Charles R; Turkovic, Lidija; Rosenow, Tim et al. (2016) Metabolomic biomarkers predictive of early structural lung disease in cystic fibrosis. Eur Respir J 48:1612-1621 |
| Blackmon, Richard L; Kreda, Silvia M; Sears, Patrick R et al. (2016) Diffusion-sensitive optical coherence tomography for real-time monitoring of mucus thinning treatments. Proc SPIE Int Soc Opt Eng 9697: |
| Tyrrell, Jean; Qian, Xiaozhong; Freire, Jose et al. (2015) Roflumilast combined with adenosine increases mucosal hydration in human airway epithelial cultures after cigarette smoke exposure. Am J Physiol Lung Cell Mol Physiol 308:L1068-77 |
| Esther Jr, Charles R; Coakley, Raymond D; Henderson, Ashley G et al. (2015) Metabolomic Evaluation of Neutrophilic Airway Inflammation in Cystic Fibrosis. Chest 148:507-515 |
| Åstrand, Annika B M; Hemmerling, Martin; Root, James et al. (2015) Linking increased airway hydration, ciliary beating, and mucociliary clearance through ENaC inhibition. Am J Physiol Lung Cell Mol Physiol 308:L22-32 |
| Bove, Peter F; Dang, Hong; Cheluvaraju, Chaitra et al. (2014) Breaking the in vitro alveolar type II cell proliferation barrier while retaining ion transport properties. Am J Respir Cell Mol Biol 50:767-76 |
| Esther Jr, Charles R; Boucher, Richard C; Johnson, M Ross et al. (2014) Airway drug pharmacokinetics via analysis of exhaled breath condensate. Pulm Pharmacol Ther 27:76-82 |
| Mellnik, John; Vasquez, Paula A; McKinley, Scott A et al. (2014) Micro-heterogeneity metrics for diffusion in soft matter. Soft Matter 10:7781-96 |
Showing the most recent 10 out of 229 publications
