MEDICAL RESEARCH Stem cell therapy for cystic fibrosis?

For 15 years, scientists have been looking for ways to correct the genetic error.
PITTSBURGH POST-GAZETTE
Researchers in Pittsburgh and Louisiana have coaxed stem cells from the bone marrow to differentiate into the type of cells that line the lungs and airways -- a proof-of-principle experiment that may lead to new therapies for cystic fibrosis.
The research team led by Dr. Jay Kolls also showed that the airway epithelial cells derived from people with cystic fibrosis could be genetically modified to restore an important cellular function.
"We have a ways to go" before a clinical trial to treat people with cystic fibrosis is possible, said Dr. Kolls, chief of the pediatric pulmonology division at Children's Hospital.
But the findings, published in this week's Proceedings of the National Academy of Sciences, suggest it may be possible to harvest stem cells from the bone marrow, grow them in cell cultures to produce epithelial cells and then transfer therapeutic genes into the cells before implanting the cells in the patient's airway.
About the disorder
Cystic fibrosis is the most common, fatal genetic disorder in Caucasians. People with the disease produce thick mucus that builds up in the airway and increases the risk of infections.
Since the 1989 discovery of the gene primarily responsible for cystic fibrosis, scientists have been looking for ways to correct the genetic error. But it has proven difficult to transfer a good copy of the gene, called CFTR, directly into the cells of a patient.
It appears easier to transfer the genes into cells when they are in culture in a laboratory dish. By using airway epithelial cells that have been derived from the patient's own stem cells, doctors could be assured that the cells wouldn't be rejected when they are ultimately transferred into the patient's lungs.
Earlier this fall, a group at Johns Hopkins University reported that they had cultured marrow stem cells on one side of a membrane and epithelial cells on the other side to produce a tissue containing mucus-producing epithelial cells. Such an engineered tissue might be used to repair or replace a damaged windpipe.
Dr. Kolls believes his experiments, which began when he was on the faculty of Louisiana State University, show that the stem cells not only stimulate epithelial cells to grow, but actually take on the shape and characteristics of the epithelial cells. The stem cells were placed in a culture with mature epithelial cells for 14 days.
Some of the stem cells were obtained from normal individuals, but some stem cells also were obtained from three people with cystic fibrosis. Dr. Kolls, who joined the University of Pittsburgh School of Medicine last year, said good copies of the CFTR gene were transferred into the epithelial cells derived from those stem cells. The transferred CFTR genes, as hoped, restored the ability to channel chloride out of the cells, a functionality lacking in cystic fibrosis patients.