Model shows emphysema might be reversed with injection of healthy lung endothelial cells

Diagram of lungs

The endothelial cells that line the blood vessels in the lung may hold the key to treating emphysema in mice, according to a study published in the Journal of Experimental Medicine.

In mice with an induced form of the disease, researchers found that changes in the activity of certain genes in lung endothelial cells, as well as the loss of those cells, closely tracked declines in lung function and other standard markers of emphysema progression. By contrast, they found that changes in epithelial cells, which line the outer surface of airways, tracked disease progression much less tightly.

Researchers then showed that an infusion with tens of thousands of healthy lung endothelial cells from genetically identical mice could prevent and/or reverse most of the profound lung damage that was seen in untreated mice. And injecting other cell types, including endothelial cells from other tissues, was not effective.

The researchers reasoned that this treatment effect might have to do with differences in the molecules secreted by diseased versus healthy lung endothelial cells. Further investigations uncovered sharp increases in the production of LRG1, a protein responsible for new blood vessel growth that has been linked to other diseases. When the researchers deleted the gene for LRG1 from lung endothelial cells in mice, the animals’ lungs were largely protected from the lung damage of induced emphysema, much as they had been by the endothelial cell therapy. The study was funded by NHLBI.

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