Their results are 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 senior author Massimo Trucco, M.D., director of the Division of Immunogenetics at Children’s Hospital and Hillman Professor of Pediatric Immunology at Pitt School of Medicine. The islet cells were isolated from genetically altered pigs produced by Revivicor Inc., a Blacksburg, Va.-based regenerative medicine company. The company, of which UPMC is a shareholder, is a long-time collaborator of Dr. Trucco and UPMC is a shareholder. 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 one 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 three months in four out of five subjects. One monkey was followed for more than one 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.
Co-authors of the paper include researchers from Erasmus University Medical Center Rotterdam, The Netherlands; Revivicor, Inc.; and Austin Research Institute, Heidelberg, Australia. The study was funded by the U.S. Department of Defense.
About Children’s Hospital of Pittsburgh of UPMC
Renowned for its outstanding clinical services, research programs and medical education, Children’s Hospital of Pittsburgh of UPMC has helped establish the standards of excellence in pediatric care. From ambulatory care to transplantation and cardiac care, talented and committed pediatric experts care for infants, children and adolescents who make more than 500,000 visits to Children’s and its many neighborhood locations each year.
Children’s also has been named consistently to several elite lists of pediatric health care facilities, including ranking eighth among children’s hospitals (FY 2006) in funding provided by the National Institutes of Health, and is named one of the top pediatric hospitals in the United States by U.S. News & World Report. For more information about Children’s Hospital, visit www.chp.edu.
About the University of Pittsburgh School of Medicine
As one of the nation’s leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997 and now ranks fifth in the nation, according to preliminary data for fiscal year 2008. Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region’s economy. For more information about the School of Medicine, visit www.medschool.pitt.edu.
About Revivicor Inc.
A leading regenerative medicine company focused on providing a superior-quality, safe, high-volume, alternative tissue source as a solution for the critical shortage of human-compatible tissues, cells, and organs. Revivicor is headquartered in Blacksburg, VA, a private company, with UPMC as a major shareholder, also has pre-clinical laboratories in Pittsburgh, PA. Technology platforms are based on the genetic modification of pigs for use in treatment of diabetes, organ transplantation, and production of medical devices for human therapeutic applications. The first group to clone pigs, and also the first in the world to produce genetically altered pigs which lack a pig gene, alpha-gal, which makes donor tissues and cells more amenable to human transplants without rejection. For more information about Revivicor visit www.revivicor.com.
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