chronic obstructive pulmonary disease

Endothelial cell treatment reverses lung damage in mice with emphysema

/ Yimy Villa / 1 Comment

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.

A new way to evade immune rejection in transplanting cells

/ Kevin McCormack / 2 Comments
Immune fluorescence of HIP cardiomyocytes in a dish; Photo courtesy of UCSF

Transplanting cells or an entire organ from one person to another can be lifesaving but it comes with a cost. To avoid the recipient’s body rejecting the cells or organ the patient has to be given powerful immunosuppressive medications. Those medications weaken the immune system and increase the risk of infections. But now a team at the University of California San Francisco (UCSF) have used a new kind of stem cell to find a way around that problem.

The cells are called HIP cells and they are a specially engineered form of induced pluripotent stem cell (iPSC). Those are cells that can be turned into any kind of cell in the body. These have been gene edited to make them a kind of “universal stem cell” meaning they are not recognized by the immune system and so won’t be rejected by the body.

The UCSF team tested these cells by transplanting them into three different kinds of mice that had a major disease; peripheral artery disease; chronic obstructive pulmonary disease; and heart failure.

The results, published in the journal Proceedings of the National Academy of Science, showed that the cells could help reduce the incidence of peripheral artery disease in the mice’s back legs, prevent the development of a specific form of lung disease, and reduce the risk of heart failure after a heart attack.

In a news release, Dr. Tobias Deuse, the first author of the study, says this has great potential for people. “We showed that immune-engineered HIP cells reliably evade immune rejection in mice with different tissue types, a situation similar to the transplantation between unrelated human individuals. This immune evasion was maintained in diseased tissue and tissue with poor blood supply without the use of any immunosuppressive drugs.”

Deuse says if this does work in people it may not only be of great medical value, it may also come with a decent price tag, which could be particularly important for diseases that affect millions worldwide.

“In order for a therapeutic to have a broad impact, it needs to be affordable. That’s why we focus so much on immune-engineering and the development of universal cells. Once the costs come down, the access for all patients in need increases.”