McGowan Institute for Regenerative Medicine
affiliated faculty member David Hackam, M.D., Ph.D. (pictured), a pediatric surgeon and scientist at Children’s Hospital of Pittsburgh of UPMC and the University of Pittsburgh School of Medicine, has received a Hartwell Biomedical Research Collaboration Award for 2011, which will provide funding toward Dr. Hackam’s goal of developing an artificial intestine.
Dr. Hackam, 2008 Hartwell Investigator, collaborating with John March, Ph.D., 2007 Hartwell Investigator and associate professor of biological and environmental engineering at Cornell University, will receive $543,571 in direct costs from The Hartwell Foundation over 3 years to pursue their proposal for the “Generation of an Artificial Intestine for the Treatment of Short Bowel Syndrome in Children.”
“Fostering collaborations between investigators of complementary scientific strengths is one of the objectives of The Hartwell Foundation Mission to fund innovative, early-stage applied biomedical research with the potential to benefit children,” said Fred Dombrose, Ph.D., president of the foundation.
Short bowel syndrome (SBS) is a condition in which the body is unable to absorb food after a significant loss of functioning intestine, which can occur from diseases such as necrotizing enterocolitis (NEC), Crohn’s disease, or birth defects where the intestine does not develop normally. Since food can’t be sufficiently absorbed by the shortened intestine, nutrients must be administered into the circulation through a vein, but many children who are fed this way can develop intravenous catheter infections and severe liver toxicity. The majority of children with SBS usually require intestinal transplantation and even liver transplantation if toxicity from the intravenous nutrition is severe. Transplantation is limited by the lack of donors and complications from immunosuppressive therapy.
To address the complications of SBS, Drs. Hackam and March have proposed building an artificial intestine using cultured intestinal stem cells from recipient intestines that can grow on a synthetic three-dimensional novel bioscaffold.
Their team will produce a bioscaffold to support the growth and differentiation of intestinal stem cells, optimizing cell growth in a three-dimensional “gut tube” reactor or artificial intestine. They will implant the tube into mice with surgically-created SBS and coat the intestine with a nutritional formula to test if the host can absorb nutrients through the artificial intestine. They also will look at the safety and effectiveness of implantation of the artificial intestine in a pig model of SBS, which is more akin to the condition seen in humans and more comparable in size.
“Dr. March and I have generated a structure that bears remarkable similarity to the normal intestine, giving us hope that we can overcome any challenges as we work to develop an artificial intestine – a novel translational therapy for children with short bowel syndrome,” said Dr. Hackam, co-director of the Fetal Diagnostic and Treatment Center at Children’s Hospital and Magee-Womens Hospital of UPMC.
Dr. Hackam was a 2008 Hartwell Investigator for his proposal, “Discovering Novel Immune Modulatory Agents Using High Content Screening in the Treatment of Neonatal Necrotizing Entercolitis.” He runs a research program at Children’s Hospital focusing on understanding the mechanisms that contribute to the development of NEC, which is the leading cause of death and disability from gastrointestinal disease in newborn infants.
Illustration: McGowan Institute for Regenerative Medicine.
Children’s Hospital of Pittsburgh of UPMC Media Relations News Release (11/28/11)
Pittsburgh Post-Gazette (11/29/11)
The Hackam Lab - Pediatric Surgery
The Hartwell Foundation
Bio: Dr. David Hackam