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Pig Pancreas Transplants Secrete Insulin, Show Durability in Diabetic Primates
By Martha Kerr
NEW YORK (Reuters Health) May 12 - Pig pancreases have been successfully transplanted into diabetic non-human primates, secreting insulin, normalizing blood glucose levels and showing promise as beta cell replacement therapy.
Results of the study by Dr. Yair Reisner of the Weizmann Institute of Science in Rehovot, Israel, and colleagues are published in an early edition of the Proceedings of the National Academy of Sciences, available online today.
Optimal beta-cell properties in the pig pancreas exist at embryonic day 42. Dr. Reisner's group previously demonstrated success with embryonic pig pancreas transplantation in diabetic mice.
The researchers now demonstrate the proof of concept of beta-cell replacement therapy with pancreatic xenotransplantation in two diabetic Cynomolgus monkeys that they followed for 393 days and 280 days after the procedure, Dr. Reisner and colleagues report.
Porcine pancreatic tissue explanted on embryonic day 42 was transplanted onto the omentum of the monkeys. Four months after xenotransplantation, there was a marked reduction in the need for exogenous insulin. By the fifth month, the animals had "full physiological control of blood glucose levels."
Dr. Reisner's team used an immunoassay specific for porcine C-peptide to show that the insulin the monkeys were producing was porcine in origin. The xenograft was predominantly vascularized with host blood vessels, "thereby evading hyperacute or acute rejection."
Proof of concept for xenotransplantation for beta-cell replacement therapy in primates has been demonstrated, Dr. Reisner declared. "It worked in mice, rats and now in monkeys. The next step is (clinical trials)," he told Reuters Health.
"Transplantation of a whole pancreas achieves a longer graft survival and functionality than isolated islets (67% after 10 years and 10% after 5 years, respectively)," the researchers say.
However, not all pancreatic functions are exhibited after transplantation. "Only the endocrine system survives long-term post-transplant," Dr. Reisner explained.
"Although further fine tuning of immune suppression, tissue dose, and implantation techniques are warranted, our results demonstrate that porcine (embryonic day 42) embryonic pancreatic tissue can correct hyperglycemia under a tolerable immune suppression protocol," the Israeli team writes.
"The long-term proliferative capacity of these grafts, their ability to induce revascularization by host endothelium, and their reduced immunogenicity, strongly suggest that porcine embryonic xenotransplantation could offer an attractive replacement therapy for diabetes."
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