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Multi-colored tangled ropes

Tackling a sticky surgical complication, Stanford researchers identify culprit and potential treatment

Abdominal adhesions can have lasting, significant consequences. Now Stanford researchers have identified the cells responsible and a possible treatment.

I recently wrote about a common, but not (at least to me) well-known complication of abdominal surgery called abdominal adhesions. I was surprised I hadn't heard much of them because these adhesions can have significant, long-term consequences — including chronic pain, female infertility and sometimes even death — and there is currently no effective treatment.

Now Jonathan Tsai, MD, PhD, a former medical student at Stanford and now a resident physician at Brigham and Women’s Hospital in Boston, and Stanford stem cell biologist and pathologist Irving Weissman, MD, have found a cellular culprit and identified a possible treatment for this condition. They published their results today in Science Translational Medicine.

As I explain in our release:

Normally the surface of our abdominal organs and the lining of our abdominal cavity are covered with a slippery membrane called mesothelium. The mesothelium allows our organs to glide smoothly past one another when we bend, twist or run.

When the mesothelium is disturbed, fibrous connections form between neighboring surfaces, ranging in severity from single threads to vast, immobilizing webs. The NIH estimates that about 93 percent of abdominal surgeries result in adhesions and that about 20 percent of surgical patients will be re-hospitalized for adhesion-related complications.

"This is a very common surgical complication, but it’s not been well-studied," Tsai said. "Until now, it wasn’t even known what cell type was involved in originating the adhesions. Now we’ve come up with a way to isolate the injured tissue before they form the adhesions, and identify the molecular pathways involved."

Tsai and Weissman, who directs Stanford's Institute for Stem Cell Biology and Regenerative Medicine and the Ludwig Center for Cancer Stem Cell Research and Medicine, studied a mouse model of adhesion formation to learn that cells of the mesothelium respond to a lack of oxygen by beginning to express specific proteins that promote the fibrous tendrils. In humans, these low-oxygen conditions are caused when tiny patches of tissue are pinched together with surgical sutures.

Intriguingly, cells in the adhesions also expressed a protein on their surface called CD47. CD47 is known as a "don't eat me" signal that protects cancer cells from elimination by the immune system.

[The researchers] found that treating the animals with antibodies that bind to mesothelin, a protein specific to injured mesothelium, significantly reduced the severity of adhesions that had already formed. Combining anti-mesothelin antibodies with an anti-CD47 antibody had an even greater effect, suggesting that roving immune cells called macrophages, which gobble up sick or dying cells, may also play a role in removing abnormal fibrous tissue.

Similar patterns of protein expression were seen in adhesions removed from human patients, suggesting that it might one day be possible to treat or prevent abdominal adhesions in humans.

Photo by Derek Bruff

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