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Growing Tissue to Help Children with Short Bowel Syndrome

Researchers at Nationwide Children’s Hospital are hoping to use short bowel syndrome patients’ own cells to grow extra tissue needed for their small intestine to function properly.

Using rat models, the team of physician-scientists found that where they incubate segments of small intestine inside the abdomen can produce tissue with different characteristics.

“Short bowel syndrome usually occurs when a surgeon is faced with the need to remove long lengths of diseased small bowel in order to save a patient’s life,” says Gail Besner, MD, chief of General Pediatric Surgery at Nationwide Children’s and senior author of the research, published in Tissue Engineering Part A and Journal of Surgical Research. “The patient cannot absorb enough nutrients post-operatively because there is not enough length of remaining small intestine.”

Short bowel syndrome can be deadly and costly. The mortality rate for children with the syndrome is 15 to 25 percent due to complications related to use of total parenteral nutrition, published research shows. This feeding method costs upwards of $100,000 per patient annually.

Moreover, the five-year survival rate for children receiving an intestinal transplant is low, largely because immunosuppression makes recipients susceptible to infections.

“The concept behind our research is to produce tissue-engineered intestine made from the patient’s own cells so that it won’t be rejected by the patient’s immune system.”

– Gail Besner, MD

“The concept behind our research is to produce tissue-engineered intestine made from the patient’s own cells so that it won’t be rejected by the patient’s immune system,” Dr. Besner says.

In one study, the researchers started with a tiny biopsy of small bowel and used it to grow organoids, which contain intestinal stem cells surrounded by myofibroblasts, fibroblasts and smooth-muscle cells. They expanded the organoids in culture several hundred-fold, and then seeded them onto tubular-shaped polyglycolic acid scaffolds to produce tissue-engineered intestine.

In another study, the researchers seeded scaffolds immediately and then implanted seeded scaffolds in five intra-abdominal locations: wrapped in intestinal mesentery, wrapped in omentum, wrapped in uterine horn membrane, attached to the abdominal wall or inserted in the subcutaneous space.

They found that seeded scaffolds wrapped in any of the first three locations, all highly vascularized membranes, produced the greatest volume and highest-quality tissue-engineered intestine after four weeks.

Immunofluorescent staining demonstrated the presence of all components of the intestine including blood vessels and elements of the enteric nervous system.

The challenge remains to fully innervate the engineered tissue so that it has the right mix of cell types needed to peristalse and absorb nutrients, Dr. Besner says.

She and her team recently received new National Institutes of Health funding to further develop the technology in a large animal model.

Liu Y, Cromeens BP, Wang Y, Fisher K, Johnson J, Chakroff J, Besner GE. Comparison of different in vivo incubation sites to produce tissue-engineered small intestine. Tissue Engineering Part A. 2018 Jan 31. [Epub ahead of print]

Cromeens B, Liu Y, Stathopoulos J, Wang Y, Johnson J, Besner G. Production of tissue-engineered intestine from expanded enteroids. Journal of Surgical Research. 2016 Jul;204(1):164-75.

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