The body is extraordinary at healing itself. However, sometimes it can be overkill. Excess scar tissue after abdominal and pelvic surgery within the peritoneal cavity can lead to serious complications and sometimes death. The peritoneal cavity has a protective layer containing organs in our stomach. It also contains fluids to keep organs lubricated. When the lining is damaged, tissue and scar tissue can form, causing problems. Researchers at the University of Calgary and the University of Bern, Switzerland, have discovered what causes excess scarring and options for trying to prevent it.
“This is of global concern. This complication of peritoneal adhesions causes pain and can lead to life-threatening small bowel obstruction and infertility in women,” said Dr. Joel Zindel, MD, University of Bern, Switzerland, and first author of a researcher working on the study as a Swiss National Science Foundation researcher at the University of Calgary. “People sometimes need a second operation.”
Research published in Science, performed on mice and showed excess scar tissue caused by macrophages, a type of white blood cell that rushes to the surgical site to begin repairing the wound.
“Joel developed a new method using very specialized imaging equipment in my lab that gives scientists a first look at what these macrophages are doing in real time,” said Dr. Paul Kubes, PhD, lead investigator of the study and professor at the Cumming School of Medicine. “We’re still working to understand why macrophages do this repair work because they are known to attack pathogens. Whatever they respond to, it’s clear their involvement is causing the scar tissue problem.”
Researchers have also found two ways to inhibit this natural response. They remove macrophages, or they introduce drugs to block macrophage stiffness. Both processes are very effective in stopping adhesion.
“We believe the macrophage response does not make the evolutionary leap to understand that surgery is beneficial and not a threat to survival,” Kubes said. “It’s possible, the body reacts to surgery, that an organ exposed to the environment is interpreted as a threat, like a predator attack. The body doesn’t understand that a surgeon will do critical repair work.”
Macrophages are also present in humans, and the research team believes that the responses seen in mice likely translate to adults and children. They hope to turn to human cell trials, soon, and eventually clinical trials.
“Every surgeon does surgery for people who have these abdominal adhesions,” says Zindel. “It is tremendous to prevent these surgical complications. This not only benefits the individual, but also creates significant savings for the healthcare system, by reducing hospital admission and surgical costs.”
Basic research is funded by the Natural Sciences and Engineering Research Council while clinical applications are funded by the Canadian Institutes of Health Research (CIHR). Kubes is supported by the Heart & Stroke and CIHR Canada Research Chairs Program and Zindel is supported by a scholarship from the Swiss National Science Foundation.
This research was made possible with support from the Nicole Perkins Microbial Communities Core Lab, the Live Cell Imaging Resource Laboratory at the Cumming School of Medicine, and the Microscopy Imaging Center (MIC) of the University of Bern.
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