Artificial Intestines Near Reality

A new artificial intestine developed in the lab could help people missing a piece of their gut.

THE GIST

A tiny artificial intestine has been made in the lab using collagen and stem cells.

Scientists are now "growing" an intestine on a larger tube structure.

Their goal is to get this artificial intestine to clinical trials in three years.

Science has given us working artificial hearts, hips, limbs and bladders, and even a trachea.

But no one has successfully created an artificial intestine, until now. A team of researchers has created a tiny one in the lab made from collagen and stem cells. They plan to scale the tube up within three years so it can be tested in human trials.

"We're going to be taking these and inserting them into animals to see if it actually works," said John March, an assistant professor of biological and environmental engineering at Cornell University who developed the artificial intestine structure.

March is developing the artificial intestine with Dr. David Hackam, a pediatric surgeon and scientist at Children's Hospital of Pittsburgh, and the University of Pittsburgh School of Medicine who specializes in treating bowel disorders.

The artificial intestines could be used to help treat those with severe bowel disorders, including approximately 25,000 children worldwide born with a condition called short bowel syndrome who are missing a piece of intestine. These patients require feeding tubes, and the rate of rejection for an intestinal transplant from another human is nearly 40% after one year, according to Dr. Hackam. "Death from rejection as well as overwhelming infection remain unacceptably high," he said.

The small artificial intestine that they have produced is based on a tissue matrix that March originally constructed to see bio-engineered bacteria working in real time without having to kill a mouse. March said he's used several different biomaterials for the matrix. Most recently he used collagen, which he says is readily available and affordable.

Special molds were used to carefully produce the tube structure, including the tiny fingerlike projections found in real intestine lining called "villi." The scientists plan to grow stem cells removed from a gut and seed them onto the tube. Eventually they envision using human cells so that a patient's cells would fill the open spaces in the "gut tube reactor," which should help prevent rejection.

"Basically the whole thing is built out of the patient's own body," March said. "We're just giving it a place to grow."

Since the tiny artificial intestine works in a test tube, the focus now is making one to test in mice, and then larger animals like pigs. It won't be easy. Replicating soft structure of the intestine as well as the numerous villi present significant challenges.

"These finger-like projections are really quite tall and have a high aspect ratio meaning that they have a curve, and then they're much higher than they are wide," March said.

The projections also have an orientation, so they need to be put on a shape that guides the cells into the right place. Nanotechnology centers can produce nano-sized structures, but human villi are measured in millimeters, which requires an "in-between" engineering technology, March said.

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The artificial intestine project is funded with a half-a-million dollar grant from the Hartwell foundation, an organization that funds biomedical research to benefit children. At the end of three years, the two scientists hope to have an artificial intestine ready for large animals. From there, Dr. Hackam said, they will secure additional funding for human trials.

Dr. Daniel Teitelbaum, a pediatric surgeon who teaches at the University of Michigan and directs the Intestinal Failure Program, calls Dr. Hackam and John March's bioengineering approach unique compared to other research efforts that include stretching the intestine and growth hormone experimentation.

The challenges to making a viable artificial intestine significant, but Dr. Teitelbaum said he's confident that the team will overcome them. "They're bright investigators," he said. "I'm following their work very closely."

"People are trying to build every single organ artificially," Teitelbaum said. "If one could really build a fully competent intestine, I think what would be incredible about it would be that this could treat thousands of patients."

Dr. Hackam said that they have two possible approaches to make sure blood gets to the artificial intestine. One is to simulate blood vessels by modifying the tube structure. Another is to try enveloping the artificial intestine in a fatty section covering the abdominal organs that has been proven to supply blood to implants there.

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