Research funded here for artificial intestine

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As a pediatric surgeon and scientist, David Hackam has had to deal with the suffering and often the deaths of children with short bowel syndrome, a condition in which the body is unable to absorb food after a significant loss of functioning intestine.

Dr. Hackam, of Children's Hospital of Pittsburgh of UPMC and the University of Pittsburgh School of Medicine, has been frustrated by the fact most SBS patients require transplants to live but significantly widespread treatment is deterred by a lack of donors and complications from immunosuppressive therapy.

That's why Dr. Hackam hopes to develop an artificial intestine that would not only benefit SBS patients but adults with intestinal problems. He said he hoped the process could be used to replace other failing organs.

And now, with the receipt of $543,571 of direct funding for three years of research from the Hartwell Foundation, Dr. Hackam and his collaborator, John March, associate professor of biological and environmental engineering at Cornell University, hope to make their dream a reality.

"If this works, it is going to be amazing," Dr. Hackam said. "Artificial organs are kind of the Holy Grail. It works in science fiction, and now we hope to do it in real life.

"For families who have a child with this, their whole world is turned upside down. They are so excited to have a child and then they learn their child has this and ... their lives go from incredible joy to incredible sadness to incredible uncertainty, often within hours.

"To be able to offer them something to get them back on track is incredibly humbling and that is what we hope to do."

Their research involves producing a synthetic three-dimensional bioscaffold upon which to grow cultured intestinal stem cells from the patient. Mr. March, who holds a doctorate in chemical engineering, has overseen the production of the bioscaffold; over the past three years Dr. Hackam has worked on optimizing the growth of stem cells.

Now with the Hartwell Foundation funding, the researchers can work to optimize the growth of intestinal stem cells in the three-dimensional "gut tube" reactor, or artificial intestine. The next step will be to implant the tube into mice with surgically created SBS and to coat the intestine with a nutritional formula to test if the host can absorb nutrients through the artificial intestine.

After that, they will implant the tube into a pig with SBS, which would be more akin to the condition in humans and more comparable in size.

"We hope we can do the animal experiments in a few years and we'd like to see it in humans in five years," Dr. Hackam said. "We're very excited and feel the field will find it very exciting."

SBS can occur from diseases such a necrotizing enterocolitis (NEC), Crohn's disease or birth defects. At any time, about 5,000 children suffer from SBS, Dr. Hackam said. About 20 percent of all premature births develop NEC, which is the fifth-leading cause of death of children.

"Now we have nothing to offer them other than transplantation, and many won't live long enough to get a transplant," he said. "So if we can create an artificial organ based on their own stem cells it would be an incredible gift to give them and their families and that is why I am so optimistic and also so humbled."

Moreover, he said, in addition to helping SBS patients, development of an artificial intestine could also benefit adults with intestinal disease. Additionally, He said the science of "crossing the threshold of generating an artificial organ" could be adapted to replace other failing organs.

The work would not be possible without the funding support the researchers received from the Hartwell Biomedical Research Collaboration Award, said Dr. Hackam, who runs a research program at Children's that focuses on understanding the mechanisms that contribute to the development of NEC. He also was a Hartwell investigator in 2008 for research on neonatal NEC.

"We need foundations to take risks to support this type of research. This foundation specifically funds work for children at high risk. Typically, funding agencies like the National Science Foundation and the National Institutes of Health provide funding mostly when you're a little closer to having a clinical product.

"This research is potentially high risk but has high return. We hope and expect this approach is going to work and will help thousands of children."


Michael A. Fuoco: mfuoco@post-gazette.com or 412-263-1968.


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