Presented to the AACT 2015 Conference

Cystic fibrosis (CF) is an inherited, fatal disease in which the cystic fibrosis transmembrane receptor (CFTR) gene is mutated, resulting in a defective CFTR sodium-chloride pump. Inefficient CFTR results in a dysregulated balance of sodium and chloride ions across membranes, causing an increase mucous viscosity and susceptibility to gastrointestinal obstruction, pancreatic insufficiency, ultimately leading to failure to thrive. Clinically, major strides have been made in caring for individuals with CF allowing management of many of the clinical issues associated with CF, extending life expectancy into the third trimester. However, despite new developments in small molecule correctors and CFTR expression enhancers, which work at the CFTR defect itself, pulmonary bronchiectasis, bacterial colonization and the ensuing inflammatory response continue to contribute to lung congestion, pulmonary failure, decreased quality of life and death in CF patients. Human adult mesenchymal stem cells (hMSCs) are multi-potent cells capable of both regenerative and medicinal capacity. hMSCs respond to their environment as well as secrete bioactive molecules that are anti-inflammatory, anti-microbial, angiogenic, chemotactic, anti-apoptotic, and anti-scarring making them bioactive resources for clinical applications. hMSCs have been used clinically in a variety of other disease in both adults and children without adverse events making them a good candidate for cell-based therapy applications in CF. Our work has established the therapeutic benefit of hMSCs to manage CF pathogenesis in the pre-clinical model of CF lung infection and inflammation. We have been able to establish that the hMSCs not only decreased inflammation they also aided in bacterial clearance. The results of the pre-clinical data have pushed the evaluation of hMSCs safety and toxicity in a phase I clinical trial at our institution. Our new pre-clinical data supports the therapeutic use of hMSCs in CF which support our group’s mission to provide new and safe therapeutics to treat CF, as well as other pediatric lung diseases associated with infection and/or inflammation.