Sean Vincent Murphy, PhD

Developing a Cell Therapy for Cystic Fibrosis

Stem cells in amniotic fluid called fetal stem cells may one day be used to treat babies born with cystic fibrosis (CF). Sean Vincent Murphy, PhD, is using an American Lung Association Senior Research Training Fellowship grant to develop cell therapy that can be used to improve the function of abnormal lung cells in CF patients.

“We’re ‘working out’ the cells so they’re tough enough to survive in the lung environment.”
Patients with cystic fibrosis have a defect in a gene that allows for proper regulation of salts and water in various tissues. This alteration causes significant problems in the lungs of people with CF. The normal mucus in the lungs becomes thick and dehydrated, and ultimately blocks the airway passages, resulting in a predisposition towards chronic bacterial infections and lung disease.

Dr. Murphy and colleagues have discovered a small number of stem cells in amniotic fluid and placental tissue, called fetal stem cells, which represent an intermediate stage between embryonic stems cells and adult stem cells. Fetal stem cells give rise to many of the specialized cell types found in the human body. They are easily obtainable, since they are found in leftover birth tissue, and can be grown in large quantities—they typically double in number every 36 hours.

The researchers will first attempt to produce functional lung fluid exchanging cells from fetal stem cells. “We will prepare cells for the stresses they will face when they get into the lungs,” Dr. Murphy says. “We place them on a flexible surface that is stretched in a way that’s similar to how lungs stretch during breathing. We’re ‘working out’ the cells so they’re tough enough to survive in the lung environment.”

They will then try to replace the function of lung cells damaged by experimental radiation with fetal stem cells, to see if they can significantly improve function to the dysfunctional lung. They performed studies in which they gave mice a dose of radiation to damage their lung cells. They found that when they administered fetal stem cells through a tube via the trachea or nose, a significant number of cells were successfully implanted in the lungs.

Dr. Murphy says that if the treatment is eventually found to be safe and effective in humans, the treatment could be given to newborns known to have cystic fibrosis through a tube down the trachea—the same type of tube used to inflate the lungs of newborns who are having difficulty breathing.

ldquo;If we were to use the babies’ own cells, we would use gene therapy on the stem cells to repair the damage and then return them to the patient,” he says. “However, we wouldn’t necessarily need to use the patients’ own cells—we can develop large banks of fetal stem cells to be used when they are needed.”