Credit: Supplied by Kubes’ Lab, Snyder Institute of Chronic Diseases, Cumming Medical School, University of Calgary
The body is amazing at healing itself. However, sometimes it can overdo it. Excessive scarring after abdominal and pelvic surgery within the peritoneal cavity can lead to serious complications and sometimes death. The peritoneal cavity contains a protective lining that contains organs inside our abdomen. It also contains fluids to keep organs lubricated. When the lining is damaged, tissue and scarring can form, which leads to problems. Researchers at the University of Calgary and the University of Bern, Switzerland, have explored the cause of excessive scarring and options for trying to prevent it.
This is a global concern. Complications from these peritoneal adhesions cause pain and can lead to life-threatening small intestine obstruction and infertility in women, ”says Dr. Joel Zindel, MD, University of Bern, Switzerland, and the first author on the study who worked on this research as a research fellow. At the Swiss National Science Foundation at the University of Calgary. “People sometimes need a second surgery.”
The research has been published in Science, Was performed on mice and shows that excess scarring is caused by macrophages, which are a type of white blood cells that rush to the site of surgery to start repairing the injury.
“Joel developed a new method using highly specialized imaging equipment in my lab that gave scientists the first look at what these macrophages are doing in real time,” says Dr. Paul Coppes, lead researcher on the study and professor at the Cumming School of Medicine. “We are still working to understand why the macrophages perform this repair because they are known to attack pathogens. Whatever their response, it is clear that their participation causes the problem of scarring.”
Researchers have also discovered two ways to block this natural response. They either removed macrophages, or administered medication to prevent macrophages from attaching to macrophages. Both processes were very effective in stopping adhesions.
“We think that the macrophage response did not make an evolutionary breakthrough in understanding that surgery is beneficial and not a threat to survival,” says Cubes. “It is possible that the body reacts to surgery, and that exposure of organs to the environment is interpreted as a threat, such as an attack from a predator. The body does not understand that the surgeon will do critical repair work.”
Macrophages are also found in humans, and the research team believes that the response shown in mice is likely to translate into both adults and children. They hope to move on to human cell trials, soon, and eventually to clinical trials.
“Each surgeon operates on people with adhesions in the abdomen,” says Zindel. “It would be surprising if we could prevent these surgical complications. Not only would it benefit individuals, it would also bring significant savings to the healthcare system, by reducing hospital costs for re-admission and surgery.”
The primary research was funded by the Council for Research in Natural Sciences and Engineering while the clinical application was funded by the Canadian Institutes of Health Research (CIHR). Kubes is supported by Heart & Stroke and the CIHR Canada Research Chairs program, and Zindel is supported by a fellowship from the Swiss National Science Foundation.
This research was possible with support from the Nicole Perkins Laboratory of Basic Microbial Communities, the Living Cell Imaging Resources Laboratory at the Cumming Medical School, and the Microscopy Imaging Center (MIC) at the University of Bern.