By isolating transient stem cells that can grow the two main types of lung tissue, an international team of researchers have partially restored the damaged lungs of mice, bringing hope for the possibility of human lung repair1.
Our lungs are susceptible to a range of diseases. Currently, the only treatment for damaged lungs is a transplant, for which demand greatly outstrips supply.
The lungs are thus a prime target for the emerging regenerative medicine field, but “there is currently a dearth of regenerative therapies for lung diseases,” notes Kyle Loh from the Stanford University School of Medicine in the USA, who jointly directed the work.
This gap in medical science exists because adult stem cells' ability to mature into cells from different tissues decreases as they age. Scientists had previously only been able to isolate stem cells that produced either — but not both — of the two major lung tissue types: one is found in the airways that transport air, and the other makes up the alveoli, where carbon dioxide in the blood is exchanged with inhaled air.
Now, Bing Lim of the A*STAR Genome Institute of Singapore and colleagues have shown that a single population of stem cells derived from mouse embryos can produce both tissue types. They also demonstrated that the stem cells can be used to repair damaged lungs in mice.
Lung stem cells extracted in an early lung development stage were grown in the laboratory. The researchers generated 100 billion billion (i.e. 1020 or about 10 million times the number of cells in the body of an adult human) new lung stem cells over six months.
They then tested whether these stem cells could regenerate lung tissue after damage to the lungs.
To achieve this, the team had to find a safe and easy way to deliver the cells. They did this by getting the mice to inhale a droplet of liquid containing the lung stem cells.
“On injection into the toxin-injured lungs of laboratory mice, the lung stem cells could regenerate new airway and alveolar lung tissue,” says Loh. “The critical advance of the paper was that both cell types were regenerated,” he notes.
“In the future, we hope that lung stem cell transplantation can be used to regenerate new lung tissue [in humans] in vivo,” he adds, but notes that they first have to test the safety and efficacy in animal models of end-stage lung disease.
The team also plans to extend their lab work to human cells to see whether they can identify equivalent stem cells that can regenerate both kinds of lung tissue.
The A*STAR-affiliated researchers contributing to this research are from the Genome Institute of Singapore. For more information about the team’s research, please visit the Stem Cell & Developmental Biology Group webpage.
- Nichane, M., Javed, A., Sivakamasundari, V., Ganesan, M., Ang, L. T. et al. Isolation and 3D expansion of multipotent Sox9+ mouse lung progenitors. Nature Methods 14, 1205−1212 (2017).| Article