Cell models are instrumental for studying basic and applied aspects of gene and molecular therapy for cystic fibrosis (CF). Human airway epithelial cell cultures maintained at an air-liquid interface and displaying mucociliary differentiation similar to the in vivo epithelium faithfully reproduce high resistance to gene therapy vectors characteristic of the native human mucosa. There cultures facilitate understanding vector interaction with target cells and provide a strong platform for pre-clinical studies vital 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 Core has focused on providing human airway epithelial cell cultures to UNC CF Center investigators. The present application will support continuing essential services and will increase the range of services to the University -wide gene and molecular therapy community. The Core provides human airway epithelial cells in environments more representative of in vivo conditions, supports relevant in vivo models and supplies additional cell types including progenitor cells. To accomplish these goals, we propose the following specific aims;1) to provide normal and CF human and mouse airway epithelial cells in model systems reproducing important elements of the in vivo airway environment, 2) to cost effectively provide additional lung cell types that are high priority targets for the UNC gene and molecular therapy community, and 3) to cost effectively provide liver and intestine cell types under investigation by the UNC gene and molecular community. Through these functions, and in conjunction with the other Cores in this application, the Cell 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
5P30DK065988-07
Application #
8051617
Study Section
Special Emphasis Panel (ZDK1)
Project Start
Project End
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
7
Fiscal Year
2010
Total Cost
$159,609
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Muhlebach, Marianne S; Zorn, Bryan T; Esther, Charles R et al. (2018) Initial acquisition and succession of the cystic fibrosis lung microbiome is associated with disease progression in infants and preschool children. PLoS Pathog 14:e1006798
Cholon, Deborah M; Gentzsch, Martina (2018) Recent progress in translational cystic fibrosis research using precision medicine strategies. J Cyst Fibros 17:S52-S60
Porrello, Alessandro; Leslie, Patrick L; Harrison, Emily B et al. (2018) Factor XIIIA-expressing inflammatory monocytes promote lung squamous cancer through fibrin cross-linking. Nat Commun 9:1988
Trimble, Aaron T; Whitney Brown, A; Laube, Beth L et al. (2018) Hypertonic saline has a prolonged effect on mucociliary clearance in adults with cystic fibrosis. J Cyst Fibros 17:650-656
Panganiban, Ronald A; Sun, Maoyun; Dahlin, Amber et al. (2018) A functional splice variant associated with decreased asthma risk abolishes the ability of gasdermin B to induce epithelial cell pyroptosis. J Allergy Clin Immunol 142:1469-1478.e2
Muhlebach, Marianne S; Hatch, Joseph E; Einarsson, Gisli G et al. (2018) Anaerobic bacteria cultured from cystic fibrosis airways correlate to milder disease: a multisite study. Eur Respir J 52:
Ghaedi, Mahboobe; Le, Andrew V; Hatachi, Go et al. (2018) Bioengineered lungs generated from human iPSCs-derived epithelial cells on native extracellular matrix. J Tissue Eng Regen Med 12:e1623-e1635
Livraghi-Butrico, Alessandra; Wilkinson, Kristen J; Volmer, Allison S et al. (2018) Lung disease phenotypes caused by overexpression of combinations of ?-, ?-, and ?-subunits of the epithelial sodium channel in mouse airways. Am J Physiol Lung Cell Mol Physiol 314:L318-L331
Chen, Gang; Volmer, Allison S; Wilkinson, Kristen J et al. (2018) Role of Spdef in the Regulation of Muc5b Expression in the Airways of Naive and Mucoobstructed Mice. Am J Respir Cell Mol Biol 59:383-396
Goralski, Jennifer L; Wu, Dan; Thelin, William R et al. (2018) The in vitro effect of nebulised hypertonic saline on human bronchial epithelium. Eur Respir J 51:

Showing the most recent 10 out of 133 publications