fibrosis is a mysterious and deadly disease that scars the lungs and
obstructs breathing. It affects about 100,000 people in the United States.
disease often is called idiopathic pulmonary fibrosis because, in most
cases, the cause cannot be found. While the prognosis is unpredictable,
patients typically survive only three to five years after diagnosis,
according to the U.S. National Library of Medicine.
‘Pulmonary fibrosis results from the failure of special lung stem cells, known as AEC2s, that help airways recover from injury.’
Cedars-Sinai investigators have pinpointed a major cause of pulmonary
fibrosis. The disease, which has no known cure, appears to
result from the failure of special lung stem cells that help airways
recover from injury, the investigators reported in the journal Nature Medicine
The study is a major step toward understanding and one day treating
"Pulmonary fibrosis slowly robs patients of breath and finally life," said Paul W. Noble,
professor and chair of the Department of Medicine and director of
the Women's Guild Lung Institute at Cedars-Sinai. "In our study, we
identified novel potential pathways to finding treatments for this
relentless disease." Noble was the study's principal investigator.
The investigators focused on alveoli, the small air sacs at the ends
of lung airways. In the alveoli, oxygen and carbon dioxide are
exchanged with blood during respiration. Epithelial cells that line the
alveoli also make a substance that helps keep the airspaces open. In
pulmonary fibrosis, these epithelial cells become abnormal, and fibrous
tissue builds up in the lungs, causing severe scarring. Researchers
don't know why this scarring process happens.
The Cedars-Sinai research team found an answer in special stem cells
known as AEC2s that are found in adult lungs and are critical to
repairing and regenerating epithelial cells. When viral infections,
pollution or other injuries damage lung tissue, AEC2 cells come to the
In people with pulmonary fibrosis, something goes wrong with AEC2
cells, the study found. Compared with lung tissue of disease-free
individuals, lung tissue from patients with pulmonary fibrosis had far
fewer AEC2 cells, and those that remained were less able to renew
themselves. Surfaces of these cells had lower concentrations of
hyaluronan, a chemical substance that promotes tissue repair and
renewal. Further, in laboratory mice, the team found that by deleting
this substance, they could produce the type of scarring found in
pulmonary fibrosis after lung injury.
"These findings are the first published evidence that idiopathic pulmonary fibrosis is primarily a disease of AEC2 stem cell failure," said Carol Liang,
assistant professor of Medicine at Cedars-Sinai and the study's
first author. "In further studies, we will explore how the loss of
hyaluronan promotes fibrosis and how it might be restored to cell
surfaces. These endeavors could lead to new therapeutic approaches."
One promising approach may be to develop drugs that stimulate the
reproduction of AEC2 cells in the lungs of patients who lack enough of
these cells, Noble said. "The exciting aspect is that we have learned
how to isolate these stem cells from diseased lungs. We can use these
cells to create tiny 'lungs in a dish' as tools for drug development,"
In an accompanying commentary in Nature Medicine
, Paul F.
Mercer and Rachel C. Chambers from the University College
London in England noted another novel finding from this study. They said
it identifies a new link between innate immune receptors, which help
mobilize the immune system to fight bacterial invaders, and hyaluronan.
This link, which promotes normal AEC2 renewal, is lost in pulmonary
fibrosis, the study showed.