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Study explores tissue recovery following massive intestinal surgery

By Meg Bolton

Michael A. Helmrath, MD

Recovering from major surgery to the intestine and/or stomach requires time and substantial patience on the part of the patient. How the tissue itself adapts and changes to accomplish this feat is still not well defined.

With a five-year Mentored Clinical Scientist Development Award from the National Institute of Health, Michael A. Helmrath, MD, assistant professor of pediatric surgery at Baylor College of Medicine, hopes to answer some of those questions by studying specific secreting cells found in the gastrointestinal tract.

Some disorders of the intestine and stomach can require massive surgery called a small bowel resection. In this procedure, the surgeon removes diseased portions of the intestine, and then sews the healthy ends back together.

"The small intestine is a rapidly turning over tissue that continues to renew itself by making new cells," says Helmrath. "This ability to regenerate allows the intestine to recover after injury or surgery."

The means by which intestinal tissue adapts after a small bowel resection is currently unknown, but Helmrath believes the answer resides in the secretory cells of the intestine.

The small intestine is composed of two types of cells: absorptive or secretory. Absorptive cells, known as enterocytes, take in and digest nutrients, while secretory cells emit important elements into the blood. Secretory cells include: goblet cells, which secrete mucus; enteroendocrine cells, which secrete hormones; and Paneth cells, which secrete defensive molecules that defend against harmful bacteria.

Helmrath believes increased production of secretory cells within the intestine aids adaptation following a small bowel resection.

Helmrath tested his theory by performing small bowel resections on mice. Following surgery, the distribution of secretory cells was recorded at timed increments. An increased production of goblet, Paneth, and enteroendocrine cells was observed shortly after the procedure, supporting Helmrath's hypothesis that massive small bowel resections do result in an increased allocation of secretory cells in the intestine.

Through future research, Helmrath plans to determine if these changes may help reset sustained increases in intestinal stem cell production following small bowel intestinal resection.

Helmrath has developed additional models that reveal that early signaling by these secreting cells causes the intestine to adjust physically. He believes this signaling ultimately decides the intestine's architecture.
"Understanding the regulation of intestinal stem cell proliferation and lineage allocation will give insight to the mechanisms that can sustain increased mucosal surface area following injury and will offer numerous potential therapeutic targets," says Helmrath.

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