March 20 , 2006
Porcine islet cells offer promise for diabetic patients
BY Stephanie McNicoll
Islet cell xenotransplantation (cross-species transplantation) presents a promising near-term solution to the critically low islet cell supply for humans suffering from type 1 diabetes, according to researchers from the Emory Transplant Center, the Yerkes National Primate Research Center and the University of Alberta (Canada).
Emory/Yerkes researchers have successfully transplanted and engrafted insulin-producing, neonatal, porcine islet cells harvested by University of Alberta researchers into diabetic rhesus macaque monkeys, restoring the monkeys’ glucose control and resulting in sustained insulin independence.
This research, published in the Feb. 26 online edition of Nature Medicine, also examines the effectiveness of a co-stimulation, blockade-based immunosuppressive regimen developed at Emory and proven to have fewer toxic side effects than currently used regimens. The study provides answers to the possibility of cross-species viral transmission, a common concern of xenotransplantation in humans.
Transplantation of islet cells has been successful in reversing type 1 diabetes in humans, but the cells’ limited availability greatly inhibits the ability to meet the medical needs of more than a million Americans who have the disease. Each year, only 3,000–4,000 donor organs are available, and each organ can only produce enough cells for, at most, one transplant.
“To meet the needs of millions of people suffering from type 1 diabetes, we must find new donor sources to allow large-scale application of islet cell transplantation in humans,” said Christian Larsen, director of the Emory Transplant Center and a Yerkes affiliate scientist. “While there is much work to be done, these studies suggest the rejection response to porcine islets can be surmounted.”
While the Emory/Alberta findings are similar to those of recently publicized research conducted by the University of Minnesota, the nonhuman primates in this study exhibited improved glucose control and sustained insulin independence using the simpler, less toxic costimulation blockade-based regimen developed by Larsen and colleague Kenneth Cardona at the transplant center and Yerkes.
Belatacept, a key ingredient in the co-stimulation blockade regimen that selectively blocks the second of two cellular signals (costimulatory signals) the body needs to trigger an immune response, was developed by investigators at Bristol Myers-Squibb Pharmaceutical Research Institute and by Larsen and Thomas Pearson of the Emory Transplant Center.
In addition, researchers addressed concerns of the possibility of cross-species disease transmission as a result of xenotransplantation.
The neonatal porcine cells used in this study were harvested using a technique developed by Gregory Korbutt and Ray Rajotte of the Surgical-Medical Research Institute at the University of Alberta.
“The harvesting method is both simple and reproducible, but the significant advantage of the technique is that the neonatal islet cells retain their growth potential post-transplant,” said Rajotte, founder and director of the University of Alberta’s islet transplantation group.
Research was supported by the National Institutes of Health, the Juvenile Diabetes Research Foundation Center, Yerkes Research Center Base Grant P51-RR000165-45, the McKelvey Lung Transplant Center and the Carlos and Marguerite Mason Trust. Additional support was provided by the Canadian Institutes of Health Research, Edmonton Civic Employees Charitable Assistance Fund, Alberta Diabetes Foundation, Canadian Diabetes Association and University of Alberta Hospital Foundation MacLachlan Fund.