According to the latest issue of Science and Translational Medicine, researchers at the Stanford University School of Medicine have determined the mechanism of surgical adhesion formation and possible treatments.
After abdominal surgery, smooth organs are tied together or fixed to the abdominal wall, and abnormal fiber connections called adhesions often occur. Symptoms caused by adhesions include chronic pain, female infertility, intestinal obstruction, and occasional death. The annual cost of postoperative adhesions in the United States exceeds $1 billion.
Researchers at Stanford University have developed a mouse model of adhesion to identify cells responsible for adhesion formation. Studies have shown that antibody-based therapies can break the already formed adhesions. The researchers found that the combination of two antibodies -- one that targets adhesion-forming cells, and the other that does not eat me signaling that cancer cells use to evade the immune system -- can significantly reduce adhesions in animals. The severity of the situation.
The researchers used a mouse model to track the formation of adhesions and the pattern of gene expression produced in the mesothelium. It was found that in mice, mesothelial cells respond to hypoxia by making a protein called HIF1α, which in turn promotes the expression of other proteins necessary for adhesion formation. When the researchers treated mice with a small molecule that inhibits HIF1α activity, the degree of adhesion produced was significantly reduced.
The study also found that treatment of animals with antibodies that bind to mesothelin, a damaged mesangial cell-specific protein, significantly reduced the severity of established adhesions. Combining anti-mesothelin antibodies with anti-CD47 antibodies has a greater effect, suggesting that flow immune cells called macrophages engulf diseased or dying cells and may also play a role in removing abnormal fibrous tissue. .
Finally, the researchers analyzed adhesion samples removed from the human body and found that human tissue expressed many of the same genes and used biological pathways similar to those found in mice. Researchers believe that similar antibody treatments can also help prevent or treat the formation of human adhesions.
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