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New Grant Allows Children's Hospital of Pittsburgh Scientists To Study Potential Source of Islet Cells as Diabetes Cure

Genetically altered pigs would serve as source for xenotransplantation of islet cells

A Children's Hospital of Pittsburgh scientist has received a $1.8 million grant from the Juvenile Diabetes Research Foundation (JDRF) to further his research of islet cell transplantation in search of a cure for diabetes.

Massimo Trucco, MD, director of Immunogenetics at Children's, and his team of researchers, in close collaboration with the Thomas E. Starzl Transplantation Institute, are genetically altering islet cells in the laboratory that someday could be transplanted into patients with Type 1 diabetes.

Islet cells produce insulin, a hormone that helps the body use glucose for energy. Researchers at Children's hope that successful islet cell transplantation will allow diabetics to live without daily shots of insulin. In other studies, human islet cells found in the pancreas have been transplanted into diabetics, but the recipients' immune systems eventually have rejected these transplanted cells.

Dr. Trucco's laboratory is developing genetically altered islet cells, grown in pigs, which do not reject when transplanted into primates. The JDRF grant will allow Dr. Trucco to further research these islet cells grown in genetically altered pigs. The pigs are created by "knocking out," or eliminating, the gene in pigs responsible for the expression of certain sugars on pig cells that cause hyperacute rejection once transplanted in humans and non-human primates. This gene, is known as alpha 1,3 galactosyltransferase (GT), is knocked out using toxins to kill the cells carrying the gene.

"Currently, islet cell transplantation isn't feasible, especially for children, because of the issue of rejection. In order to combat the rejection that occurs after transplant, patients need to take heavy doses of anti-rejection medication that can have harmful long-term side effects including kidney failure," Dr. Trucco said. "Our ultimate goal is to further genetically alter our pigs to make them more similar to humans. Their organs, cells and tissues will be available for transplant without the need for immunosuppression in young diabetics."

In addition to rejection, human islet cell transplantation is further complicated by the national organ shortage. Two human pancreases are needed to obtain enough islet cells for transplant and there are more than 1,600 people nationwide currently waiting for a pancreas transplant.

Dr. Trucco's JDRF grant is a three-year grant that includes three projects: the isolation and gene therapy of pig islet cells, the modification of these cells to prevent rejection and the xenotransplantation of these cells from pig to primate.

Dr. Trucco, is an internationally recognized diabetes researcher. In 1994 in the journal Nature, his lab published results of a study concluding that one or more viruses triggered the onset of diabetes. He later published a study that announced Coxsackievirus B produces a superantigen that, in genetically predisposed children, incites an immune response that can trigger the onset of type 1 diabetes.

Marc Lukasiak or Melanie Finnigan, 412-692-5016, or

Last Update
February 19, 2008
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Last Update
February 19, 2008