Certain Lung Cells Seen to Reverse Emphysema in Preclinical Study

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by Forest Ray PhD |

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Injecting mice with healthy lung endothelial cells — specialized cells lining the inside of blood vessels — prevented, and in some cases reversed, lung damage associated with emphysema, a severe form of chronic obstructive pulmonary disease (COPD), in a recent study.

The study, “Reversal of emphysema by restoration of pulmonary endothelial cells,” was published in the Journal of Experimental Medicine.

COPD is a chronic inflammatory disease that affects the airways. While its specific cause remains unknown, it has been strongly associated with exposure to irritants that inflame the lungs. Emphysema, in particular, is usually triggered by long-term exposure to cigarette smoke.

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One key feature of COPD and emphysema is a remodeling of lung tissue, often resulting in the progressive destruction of alveoli — the tiny air sacs that are responsible for exchanging oxygen and carbon dioxide in the lungs.

Vascular endothelial cells of the lungs, which line the inner surfaces of lung blood vessels, play a key role in tissue remodeling and overall health. Past studies have drawn links between endothelial cell dysfunction and COPD.

“However, it is not clear whether endothelial dysfunction drives COPD pathophysiology [development] or is simply the consequence of damaged alveolar surface area,” Augustine M.K. Choi, MD, the study’s co-senior author, said in a Weill Cornell Medicine press release.

To investigate the relationship between emphysema and lung endothelial cells in more detail, Choi and his colleagues from Weill Cornell Medicine and NewYork-Presbyterian hospital examined lung tissue samples taken from patients with emphysema and a COPD mouse model.

They first demonstrated that changes in both human and mouse lung endothelial cells were associated with emphysema progression, while alterations in lung epithelial cells — those that line the outer surface of the airways — were not.

Injecting COPD mice with healthy lung endothelial cells taken from genetically identical animals partially reversed signs of emphysema. Specifically, healthy lung endothelial cells appeared to promote tissue repair and regeneration, possibly by signaling cells involved in those processes to proliferate, or grow, into damaged lung areas.

Endothelial cells from tissues found elsewhere in the body, or other cell types, did not produced the same therapeutic effects as endothelial cells found in the lungs.

“Our findings could indicate that re-establishing a healthy vasculature — by either intravenous delivery of normal lung endothelial cells or reversing aberrant endothelial cell signaling — could encourage repair and regeneration of damaged lung tissue,” said Shahin Rafii, MD, co-senior author of the study.

Further examining the specific changes that might lead to COPD and emphysema progression, the team found that endothelial cells isolated from patient samples and from the lungs of COPD mice contained high levels of LRG1, a protein known to be involved in several other disorders.

Whereas LRG1 grew more active in response to COPD-inducing treatments, mice genetically modified to be unable to produce the protein specifically in their lung endothelial cells appeared to have a measure of protection against developing emphysema.

“Taken together, our data strongly suggest the critical role of endothelial cell function in mediating the pathogenesis [development] of COPD/emphysema,” said Alexandra Racanelli, MD, PhD, the study’s co-first author.

“Targeting endothelial cell biology by administering healthy lung endothelial cells and/or inhibiting the LRG1 pathway may therefore represent strategies of immense potential for the treatment of patients with advanced COPD or emphysema,” she said.