Tissue repair achieved in mouse models of inflammatory bowel disease
In a collaborative study between KU Leuven (Belgium) and Seoul National University (South Korea), researchers have developed a method to repair damaged tissues in the intestine using the patient’s own immune system. This regenerative approach may lead to a novel treatment for those with inflammatory bowel diseases, such as ulcerative colitis and Chron’s disease.
Their research was recently published in the journal Gut.
In inflammatory bowel disease, the immune system attacks the cells that line the gut, leading to inflammation and painful ulcers. Typically, inflammatory bowel disease is treated with drugs that reduce the body’s immune response and therefore limit inflammation – however this approach also hinders the immune response involved in repairing damaged areas of the intestine.
White blood cells known as macrophages play a key role in this repair process, however their mechanism of action is unknown.
To tackle this, the team examined macrophages sourced from the intestines of patients with inflammatory bowel disease.
“Our idea is that the migration of macrophages to the damaged tissue in inflammatory bowel disease is essential to stimulate its recovery,” explained lead author Gianluca Matteoli (KU Leuven).
“If the patients had acute disease, they had a lower amount of these beneficial cells, and if they went into remission, then amounts of macrophages went up. This suggests that they are part of the reparative process.”
The team found that a subgroup of these macrophages responded to prostaglandin E2 (PGE2) – a messenger molecule associated with tissue regeneration.
They then saw that macrophages were less sensitive to PGE2 in a mouse model of ulcerative colitis when compared with healthy mice. What’s more, when PGE2 levels were increased, the sensitive macrophages were activated – releasing a substance that stimulated tissue regeneration.
“We already knew that prostaglandins were important for inducing proliferation of tissue cells, but this study shows that they are also important for controlling the inflammatory effect, so moving the body from the acute stage where inflammation dominates to the reparative stage,” Matteoli commented.
When PGE2 receptors on the macrophages were knocked out, the degree of tissue regeneration was reduced.
Led by Seung Hyeok Seok (Seoul National University), the team were able to get these macrophages to ‘swallow’ liposomes containing a substance able to trigger the release of the repair stimulating agent. This implies that a new treatment could involve jump-starting the macrophages into stimulating tissue repair using therapeutic liposomes.
“We want to identify other factors that trip the switch that turns macrophages from inflammatory cells to non-inflammatory cells,” concluded Matteoli. “Then, using the liposome technology that Professor Seok has developed, these could be used to target the macrophages and so produce very precise drugs.”
Link:https://www.regmednet.com/tissue-repair-achieved-in-mouse-models-of-inflammatory-bowel-disease/
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