Study finds cause of pulmonary fibrosis in failure of stem cells that repair lungs

November 22, 2016

LOS ANGELES (Nov. 22, 2016) - Cedars-Sinai investigators have pinpointed a major cause of pulmonary fibrosis, a mysterious and deadly disease that scars the lungs and obstructs breathing. 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, which affects about 100,000 people in the U.S. The 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 slowly robs patients of breath and finally life," said Paul W. Noble, MD, 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 rescue.

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, MD, 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," he explained.

In an accompanying commentary in Nature Medicine, Paul F. Mercer, PhD, and Rachel C. Chambers, PhD, 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.
Research reported in this publication was supported by the National Institutes of Health under award numbers P01 HL108793, R01 HL060539, AI052201 and R01 HL122068; and by the California Institute for Regenerative Medicine under award number RB5- 07302.

About the Women's Guild Lung Institute

The Women's Guild Lung Institute provides outstanding care for patients with lung diseases of all kinds and at all stages. A leader in the fields of pulmonary care and research, thoracic surgery and lung cancer, the institute is dedicated to matching patients with the most effective treatments. These include the best evidence-based therapies currently available, as well as access to innovative clinical trials.

Cedars-Sinai Medical Center

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to