Patients with cystic fibrosis (CF) could potentially be treated using their own stem cells that have been manipulated by gene therapy, suggests a study reported in this weeks Proceedings of the National Academy of Sciences (PNAS). The authors, who represent five institutions, including the University of Pittsburgh School of Medicine and Childrens Hospital of Pittsburgh, demonstrate for the first time that human bone marrow-derived adult stem cells can be coaxed to differentiate into airway epithelial cells and that encoding these cells with the gene that is defective in CF restores an important cellular function essential for keeping the airways clear of mucus and air-borne irritants.
"Our results provide proof of principle that a cell-based therapy using marrow stromal stem cells is both a feasible and promising clinical approach. We plan to further investigate its potential and are hopeful that we can perform a small clinical trial within the next two to three years," noted senior author Jay K. Kolls, M.D., professor of pediatrics, immunology and molecular genetics and biochemistry at the University of Pittsburgh School of Medicine and chief, Division of Pediatric Pulmonology and Laboratory of Lung Immunolgy and Host Defense at Childrens Hospital of Pittsburgh.
CF is the most common, fatal genetic disorder affecting Caucasians and is characterized by a mutation of a gene that sits on the surface of epithelial cells, including those that line the airways in the lungs. The gene, transmembrane conductance regulator (CFTR), is responsible for channeling chloride out of cells, an essential function that influences the level of airway surface liquid. This fluid sits atop the airway cells and provides support for the hair-like projections called cilia that sweep mucus and dirt away from the cell. When the level of liquid is too low, as is the case in CF, mucus builds up and the area becomes an attractive environment for bacteria to colonize and cause infection.
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