Endothelial cell treatment reverses lung damage in mice with emphysema

Emphysema is a condition that causes damage to the alveoli, the air sacs in your lungs. The walls of the damaged air sacs become stretched out and cause your lungs to get bigger. This makes it harder to move your air in and out. It is the most common form of the condition known as chronic obstructive pulmonary disease (COPD) and is typically triggered by long-term cigarette smoking. Estimates show that approximately 200 million people around the world are affected. Unfortunately, there is no cure for this disease of the lungs.

A study conducted by researchers at Weill Cornell Medicine and NewYork-Presbyterian found that specialized endothelial cells may hold the key to treating emphysema. Endothelial cells line the inner surface of blood vessels and have been shown to play an important role in protecting and restoring the health of key organs. Specifically, lung endothelial cells line the inner surface of the lung’s network of blood vessels.

As part of their research, the team studied lung tissue from human emphysema patients while also looking at lung issue from mice with an induced form of the disease. What they found that was that changes in the activity of certain genes in lung endothelial cells and the loss of those cells was associated with decreased lung function and other indicators of emphysema progression.

The researchers then infused mice with induced emphysema with healthy lung endothelial cells from genetically identical mice and the results were astounding. The team showed that they could prevent and/or reverse most of the lung damage that was seen in untreated mice. By contrast, injecting other cell types, including endothelial cells from other tissues, did not have the same effect.

The team believes that this treatment effect might have to do with differences in the molecules secreted by diseased versus healthy lung endothelial cells. To back up this claim, they found that lung endothelial cells in both humans and mice with emphysema showed sharp increases in production of LRG1, a molecule that promotes new blood vessel growth that has been linked to retinal and kidney diseases as well as some cancers. Additionally, when the researchers deleted the gene for LRG1 from lung endothelial cells in mice, the lungs were largely protected from the lung damage of induced emphysema, much as they had been by the endothelial cell therapy.

In a news release from Cornell, Dr. Alexandra Racanelli, a co-first author on this study and an instructor of medicine in the Division of Pulmonary and Critical Care Medicine at Weill Cornell Medicine and a pulmonologist at NewYork-Presbyterian/Weill Cornell Medical Center, had this to say about the results.

“Taken together, our data strongly suggest the critical role of endothelial cell function in mediating the pathogenesis of COPD/emphysema. 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.”

The full study was published in the Journal of Experimental Medicine.

Newly Identified Stem Cells Breathe Life into Lung Disease Therapy

Breathing. So crucial to life yet so easy to take for granted—maybe because it’s one of the few functions our bodies control both unconsciously and consciously.


credit: Move Forward

But I imagine people with lung disease, such as chronic obstructive pulmonary disease (COPD) are all too aware as their continual struggle to breathe worsens over time. COPD, the third leading cause of death in both the U.S. and the world, is caused by progressive damage to the lung’s air sacs, or alveoli, which deliver the oxygen in our lungs to the blood and onto our organs. Besides a lung transplant, which is a very impractical option, there aren’t any cures a doctor can offer. Still, patients and physicians should be encouraged by the identification of a rare lung stem cell population reported on January 29th in Nature, which may point to much-needed new therapeutic approaches.


Mouse lung after flu virus-induced lung damage. In response to infection, p63+Krt5+ lung stem cells (stained blue) begin to expand and migrate to sites of injury. Credit: Nature

Previous clinical studies have observed that survivors of the sudden, widespread lung damage from acute respiratory distress syndrome (ARDS)—one of the symptoms of the H1N1 swine flu pandemic—can fully recover lung function in just six months. In this current report, collaborative research teams from Singapore and New England showed in animal studies that a lung stem cell population, dubbed p63+Krt5+, was essential for regeneration after lung damage caused by H1N1 infection. Using a sophisticated genetic technique, the team tracked these p63+Krt5+ cells following infection-induced lung damage. In 15 days after infection, and even more so by day 60, the stem cells clearly had expanded, migrated into the damaged regions of the lungs, and begun assembling into new alveoli. In non-infected animals these results weren’t observed.

To make sure these results were specifically due to the p63+Krt5+ cells, the researchers reached into their genetic toolbox again to enable them to kill off just the p63+Krt5+ cells during this experiment. Now, when the infection-induced lung damage was repeated no lung regeneration was seen, resulting in lung scarring and poor oxygen capacity in the animals. Their follow up experiment was the most intriguing: again, the p63+Krt5+ stem cell kill off and infection-induced lung damage was repeated but this time p63+Krt5+ stem cells grown in the lab were transplanted to the lungs. Following transplant, lung regeneration was restored and the stem cells matured into alveolar cells, which are components of the lung air sacs.

The existence of these lung stem cells and their role in lung regeneration is bolstered by an independent UCSF study, reporting in the same issue of Nature, that show the cells’ ability to migrate to the site of injury and contribute to healing. They include fascinating video microscopy of the stem cells’ migration into the lung tissue.

All of these results suggest a new avenue to explore for treating deadly lung diseases like COPD, which killed an estimated 3 million people worldwide in 2012. Patricia Inacio, writing for Lung Disease News, summed it up this way:

“Enhancing this ability of the lungs to regenerate after an injury can aid in the treatment of a wide range of pulmonary diseases. This study opens up new therapeutic possibilities, especially with the stem cell-based therapies for a variety of diseases.”