Fake 'intestine' may help kids feel better

A tiny 3-D collagen scaffold could offer relief to children who have lost parts of their intestines. Children with short bowel syndrome (SBS) are unable to absorb food properly and need to have nutrients administered directly into their veins, which can cause catheter infections and potentially fatal liver toxicity. The majority of children with the condition require an intestine transplant—which is limited by a lack of suitable donors and complications from immunosuppressive therapy. John March, associate professor of biological and environmental engineering at Cornell University, and David Hackam, professor of surgery at the University of Pittsburgh, are collaborating to turn a research tool engineered in March’s lab into an artificial intestine to be transplanted into children with SBS. The condition is connected to Crohn’s disease, necrotizing enterocolitis, and birth defects. Hackam had been exploring SBS treatments using intestinal stem cells but lacked a suitable artificial matrix to host the cell growth while March had developed such a matrix, but lacked access to the intestinal stem cells and the expertise in stem cell biology required for it to become a functional intestine. The researchers hope that by working together they will come up with a “gut tube reactor” that will facilitate the absorption of nutrients. Stem cells from a patient’s own intestine would be grown on a hydrogel mold and then be transplanted into the body to act as an artificial intestine. The project, funded through a grant from The Hartwell Foundation has an ambitious three-year timeline and will begin with researchers implanting the tube into mice and coating it with a nutritional formula to test if they are able to absorb the nutrients. If successful, they will then move on to pigs, which share greater similarity with humans and have larger abdominal cavities that will facilitate the scale-up of the artificial intestine to a size appropriate for humans. “The generation of artificial organs represents an absolute holy grail in medical research; a transformative approach for children with short bowel syndrome that could benefit thousands of children by reducing morbidity and mortality,” says Frederick Dombrose, president of The Hartwell Foundation. The tubes will be based on hydrogel scaffolds developed by Cornell graduate student Jiajie Yu and former postdoctoral researcher Jong Hwan Sung, as reported in the journal Lab on a Chip. Their discovery represented a breakthrough in the field, and allowed March’s lab to better study drug absorptions and bacteria in the intestine under realistic physiological conditions, rather than relying on two-dimensional cultures or live animal models. While the original models were done on a tiny scale—about 1 millimeter high and 200 microns across and only visible under a scanning electron microscope—March says the new tubes will be much larger. “It’s neat that we are going so quickly into applications of our research.”