McGowan Institute for Regenerative Medicine
faculty member Massimo Trucco, MD (pictured), director of the Division of Immunogenetics at Children’s Hospital of Pittsburgh of UPMC and Hillman Professor of Pediatric Immunology at the University of Pittsburgh School of Medicine, is the leader of a study where, for the first time, scientists have achieved survival of islet cells and normal glucose regulation without diet restrictions or insulin injections in a diabetic non-human primate for longer than 1 year. The results of the team of scientists from Children’s Hospital, the Thomas E. Starzl Transplantation Institute, and Pitt’s School of Medicine were published in the December issue of the American Journal of Transplantation.
The findings, involving genetically altered islet cells from donor pigs, are an important step toward the potential clinical application of islet cell xenotransplantation, according to Dr. Trucco. The islet cells were isolated from genetically altered pigs produced by Revivicor Inc., a Blacksburg, VA-based regenerative medicine company. The company is a long-time collaborator of Dr. Trucco. Islet cells from these pigs contain a gene that produces the human version of a cell surface protein called CD46, which plays a key role in modulating an immunological pathway that leads to immediate rejection of foreign cells.
Human islet cell transplantation has been performed for approximately a decade to treat patients with type 1 diabetes in which the body’s own immune system destroys the insulin-producing beta cells (a type of islet cell) of the pancreas. Patients with type 1 diabetes must take insulin every day to live, and the vast majority of those who have received islet cell transplants have been forced to return to insulin injections because the transplanted cells lose function within months, according to the National Institute of Diabetes and Digestive and Kidney Diseases.
“Until now, long-term survival of transplanted pig islet cells has not been achieved, clinically or in the laboratory, without significant rejection and other issues,” Dr. Trucco said. “Now, we have been able to achieve functionality of transplanted cells, and complete reversal of diabetes, for longer than 1 year in a monkey.”
In the study, Dr. Trucco and colleagues isolated the genetically altered pig pancreas cells and then transplanted them into several monkeys with diabetes by infusion into a large liver vein.
Sufficient numbers of the infused cells survived resulting in correction of blood glucose levels – without the use of insulin or diet modification – for longer than 3 months in 4 out of 5 subjects. One monkey was followed for more than 1 year and maintained normal blood sugar levels.
The gene manipulation of the cells transplanted by Dr. Trucco’s team also may have influenced the antibody-driven rejection response to foreign cells which reduced the need for immunosuppression to preserve a sufficient mass of islet cells for glucose control over the long term.
The potential use of donor cells from pigs in human islet cell transplantation also solves another hurdle, namely the lack of pancreases available for transplant, according to Dr. Trucco.
Illustration: McGowan Institute for Regenerative Medicine.
Children’s Hospital of Pittsburgh of UPMC/University of Pittsburgh Schools of the Health Sciences Media Relations News Release (12/03/09)
Children’s Hospital of Pittsburgh of UPMC News Release (12/04/09)
Pittsburgh Post-Gazette (12/03/09)
Pittsburgh Post-Gazette (12/04/09)
Pittsburgh Tribune-Review (12/04/09)
Deseret News (12/05/09)
University Times (12/10/09)
Spotlight Series: Dr. Massimo Trucco --
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Abstract (American Journal of Transplantation. December 2009, Volume 9, Issue 12, Pages 2716 – 2726)