Researchers have now identified and characterized adult stem cells that have the capacity to regenerate lung tissue. The findings, which come from studies of isolated human stem cells and of mice infected with a particularly nasty strain of H1N1 influenza virus, could lead to new regenerative therapies for acute and chronic airway diseases, according to the report published in the October 28th issue of the journal Cell, a Cell Press publication.
"This virus is as close as you can get to the one responsible for the 1918 influenza pandemic," said Frank McKeon of the Genome Institute of Singapore and the Harvard Medical School in Boston. "You get massive lung damage, infiltration of white cells, and loss of lung tissues. Two months out, the lungs miraculously look normal again."
Infections with this H1N1 strain cause acute respiratory distress syndrome, marked by extensive lung damage and low levels of oxygen in the blood. What hasn't been clear is what happens to the lungs of those who manage to survive.
The current findings in mice provide evidence that our lungs are capable of true regeneration. Stem cells found along the surfaces of the airways (in the bronchiolar epithelium) proliferate rapidly in mice after viral infection and migrate to sites of damage. Once there, the cells assemble into "pods" and switch on genes that identify them as alveoli, small hollow structures that are the sites of gas exchange in the lung.
McKeon and Wa Xian of the Institute of Medical Biology in Singapore and the Brigham and Women's Hospital in Boston were able to clone these same stem cells from human tissue. Even in a laboratory dish, they show that the human cells form into alveolar-like structures. That's despite the fact that a gene expression profile of those cells shows little difference between them and stem cells with alternate fates isolated from the upper airways.
The findings point to adult airway stem cells as an important and perhaps underappreciated ingredient in regenerative medicine, the researchers say. That's even if stem cells per se are unlikely to help much in the case of emergent infectious diseases such as influenza.
"The problem in the case of a pandemic is that people die quickly," McKeon says. "It is hard to imagine how a cell-based treatment will play in those time constraints." On the other hand, stem cell-based therapies or secreted factors identified by this study as important for lung regeneration have the potential to enhance the speed of lung regeneration. It is also possible that such regenerative therapies could aid in those with hard-to-treat conditionpulmonary fibrosis, in which lung tissue becomes scarred.
"Pulmonary fibrosis is a bad disease," McKeon said. "The question is: could you get rid of the fibrosis and replace it with real lung tissue?"
A second study in the same issue of Cell identifies molecular pathways in the lung that may also lead to new strategies for encouraging lung regeneration. In that case, researchers led by Shahin Rafii at Weill Cornell Medical College studied mice with one lung removed, a treatment that causes the remaining lung to produce more alveoli.