Severe Lung Injuries Bring About Abnormal Stem Cell Repair UCSF Study Shows

New research reveals that severe lung injuries from diseases such as COVID-19 and pulmonary fibrosis can initiate anomalous differentiation of stem cells in the lung, thus inhibiting the regaining of healthy function.

X-Ray showing severe lung damage

Jaymin Kathiriya and Chaoqun Wang report in the journal Nature Cell Biology the discovery of a novel stem cell pathway in lung damage. Severe lung injuries, such as those seen in COVID-19 and idiopathic pulmonary fibrosis (IPT), set off abnormal stem cell repair. This changes the structure of the lung and compromises its function.

Findings by the University of California San Francisco researchers confirm a trajectory seen in damaged lungs. They could help in reversing abnormal differentiation and restoring normal function in the near future.

A surprising discovery

Before now, the belief was that type 2 alveolar epithelial cells (AEC2s) in human and mice lungs are not so much different in terms of regenerative capacity. The current study shows that may not exactly be correct.

Researchers observed that human AEC2s (hAEC2s) can produce pathologic basal cells and transitional cell types. This is unlike what is seen in mouse AEC2s.

In-vitro single-cell inquiry into hAEC2s’ transdifferentiation showed the existence of transitional cell types as well as basal cell subsets. These were similar to those that have been seen in lungs affected by fibrosis.

“The first time we saw AEC2s differentiating into basal cells, it was so striking that we thought it was an error,” said Tien Peng, MD, who supervised Wang. “But rigorous validation of this novel trajectory has provided enormous insight into how the lung remodels in response to severe injury, and a potential path to reverse the damage.”

With this study, researchers could model abnormal stem cell repair – also called stem cell metaplasia – similar to that linked to a severe alveolar injury.

Providing a starting point for future research

The study provides proof of a novel stem cell trajectory that occurs in damaged human lungs. It opens the way for better understanding how lungs with severe injuries can attempt repair and end up scarring.

The gradual transdifferentiation to pathologic basal cells that were observed in the study is not peculiar to IPT. Similar is also often seen in the lungs of people with COVID-19 or scleroderma lung disease.

The findings, therefore, suggest that hACE2s play a major part in the incidence of metaplastic basal cells in diseases typified by severe alveolar injury.

With the new research, a pathway for possibly reversing abnormal lung repair through the combating of abnormal stem cell differentiation has been uncovered. The study has laid the foundation for future work that could help to dig up curative agents that would potentially help to reverse stem cell metaplasia in severe alveolar injury.