November 17, 2014
Stem Cells’ Role in Lung Regeneration Points to Possible New Therapies
Researchers have uncovered the role of certain stem cells in regenerating lungs damaged by disease,
shedding light on the inner workings of lung regeneration and pointing to potential therapeutic
strategies that harness these lung stem cells.
“The idea that the lung can regenerate has been slow to take hold in the biomedical research
community,” said Jackson Laboratory (JAX) professor Frank McKeon, Ph.D., “in part because of the
steady decline that is seen in patients with severe lung diseases like chronic obstructive pulmonary
disease (known as COPD) and pulmonary fibrosis.” Dr. McKeon led the study with JAX colleague Wa
Xian, Ph.D.
Nevertheless, there are examples in humans that point to the existence of a robust system for lung
regeneration, he added, saying that, “Some survivors of acute respiratory distress syndrome, or ARDS,
for example, are able to recover near-normal lung function following significant destruction of lung
tissue.”
Mice appear to share this capacity. Mice infected with the H1N1 influenza virus show progressive
inflammation in the lung followed by outright loss of important lung cell types. Yet over several weeks
the lungs recover, revealing no signs of the previous injury.
Using this mouse model system, McKeon and his colleagues had previously identified a type of adult
lung stem cell known as p63+/Krt5+ in the distal airways. When grown in culture, these lung stem cells
formed alveolar-like structures, similar to the alveoli found within the lung. (Alveoli are the tiny
specialized air sacs that form at the ends of the smallest airways, where gas exchange occurs in the
lung.) Following infection with H1N1, these same cells migrated to sites of inflammation in the lung and
assembled into pod-like structures that resemble alveoli, both visually and molecularly.
In the new paper, published November 12 in Nature, the research team reports that the p63+/Krt5+
lung stem cells proliferate upon damage to the lung caused by H1N1 infection. Following such damage,
the cells go on to contribute to developing alveoli near sites of lung inflammation.
To test whether these cells are required for lung regeneration, the researchers developed a novel system
that leverages genetic tools to selectively remove these cells from the mouse lung. Mice lacking the
p63+/Krt5+ lung stem cells cannot recover normally from H1N1 infection and exhibit scarring of the lung
and impaired oxygen exchange, demonstrating their key role in regenerating lung tissue.
The team also showed that when individual lung stem cells are isolated and subsequently transplanted
into a damaged lung they readily contribute to the formation of new alveoli, underscoring their capacity
for regeneration.
In the U.S., about 200,000 people have ARDS, a disease with a death rate of 40%, and there are 12
million patients with COPD. “These patients have few therapeutic options today,” Dr. Xian says. “We
hope that our research could lead to new ways to help them.”
Stem Cells’ Role in Lung Regeneration Points to Possible New Therapies
Researchers have uncovered the role of certain stem cells in regenerating lungs damaged by disease,
shedding light on the inner workings of lung regeneration and pointing to potential therapeutic
strategies that harness these lung stem cells.
“The idea that the lung can regenerate has been slow to take hold in the biomedical research
community,” said Jackson Laboratory (JAX) professor Frank McKeon, Ph.D., “in part because of the
steady decline that is seen in patients with severe lung diseases like chronic obstructive pulmonary
disease (known as COPD) and pulmonary fibrosis.” Dr. McKeon led the study with JAX colleague Wa
Xian, Ph.D.
Nevertheless, there are examples in humans that point to the existence of a robust system for lung
regeneration, he added, saying that, “Some survivors of acute respiratory distress syndrome, or ARDS,
for example, are able to recover near-normal lung function following significant destruction of lung
tissue.”
Mice appear to share this capacity. Mice infected with the H1N1 influenza virus show progressive
inflammation in the lung followed by outright loss of important lung cell types. Yet over several weeks
the lungs recover, revealing no signs of the previous injury.
Using this mouse model system, McKeon and his colleagues had previously identified a type of adult
lung stem cell known as p63+/Krt5+ in the distal airways. When grown in culture, these lung stem cells
formed alveolar-like structures, similar to the alveoli found within the lung. (Alveoli are the tiny
specialized air sacs that form at the ends of the smallest airways, where gas exchange occurs in the
lung.) Following infection with H1N1, these same cells migrated to sites of inflammation in the lung and
assembled into pod-like structures that resemble alveoli, both visually and molecularly.
In the new paper, published November 12 in Nature, the research team reports that the p63+/Krt5+
lung stem cells proliferate upon damage to the lung caused by H1N1 infection. Following such damage,
the cells go on to contribute to developing alveoli near sites of lung inflammation.
To test whether these cells are required for lung regeneration, the researchers developed a novel system
that leverages genetic tools to selectively remove these cells from the mouse lung. Mice lacking the
p63+/Krt5+ lung stem cells cannot recover normally from H1N1 infection and exhibit scarring of the lung
and impaired oxygen exchange, demonstrating their key role in regenerating lung tissue.
The team also showed that when individual lung stem cells are isolated and subsequently transplanted
into a damaged lung they readily contribute to the formation of new alveoli, underscoring their capacity
for regeneration.
In the U.S., about 200,000 people have ARDS, a disease with a death rate of 40%, and there are 12
million patients with COPD. “These patients have few therapeutic options today,” Dr. Xian says. “We
hope that our research could lead to new ways to help them.”