PI Thomas Gilbert
Title Basic and Clinical Studies of Cystic Fibrosis: Ex Vivo Model of Cystic Fibrosis
Description Cystic fibrosis (CF) affects approximately 30,000 individualsin the United States, causing an accumulation of thick, sticky mucus that adversely impacts normal mucociliary clearance. The lack of proper clearance predisposes patients to chronic pulmonary infections, injury to the conducting airways in the form of bronchiectasis and bronchiolitis obliterans, and ultimately can lead to respiratory failure. CF is the leading diagnosis in children that require lung transplantation. Considerable resources have been applied to the study of CF with the hope of developing a treatment or cure, but progress has not been as rapid as anyone would desire. In the current research environment, the only way to determine if a treatment strategy has an effect on airway function is to move from in vitro studies to clinical studies in patients, which poses a very high bar to acceptance. The primary purpose of this proposal is to develop a humanized ex vivo model of the CF airway as a means to investigate the effect of new therapies on function, including ion transport and mucociliary clearance. A bioreactor has been developed that is capable of simulating the conditions in the trachea during respiration. With the expertise from the P30, decellularized tracheas will be seeded with airway epithelial cells from patients with and without cystic fibrosis and the culture conditions will be optimized. Then testing strategies will be developed to assess airway epithelial cell function without disrupting the trachea construct and the impact of various known medical treatments on the cultures will be tested. Finally, airway tissue will be obtain from patients with and without CF, the tissue will be decellularized and seeded with airway epithelial cells to begin to understand if the composition and structure of airways in CF contributes to the dysfunction. The end result of this work will be a robust testing platform that will enable functional testing of the airway which will allow a deeper understanding of the pathogenesis of CF and more robust testing of new drug therapies.
Source NIDA Core “Center of Excellence” Grant Program
Term 06/01/11 – 05/31/13
Amount Year 1 DC: $75,000
Year 1 Total: $113,625
Total DC: $150,000
Total: $227,250