Cross-species transplant cuts diabetic monkeys’ need for insulin injections

November 14th, 2007 - 2:30 am ICT by admin  
The scientists have revealed that the new approach has the potential to eliminate the need for risky immune suppression drugs that prevent rejection.

The transplanted cells, known as primordia, became engrafted within the rhesus macaque monkeys within several weeks of the transplants. The cells also released pig insulin in response to rising blood glucose levels, as would be expected in healthy animals and humans.

“The approach reduced the animals’ need for insulin injections and has promise for curing diabetes in humans. The transplants worked without a need for immune suppression and that is a major obstacle we have overcome,” says senior investigator Dr. Marc Hammerman, the Chromalloy Professor of Renal Diseases in Medicine.

He admitted that the transplants fell short of producing sufficient insulin to cure the macaques’ diabetes, but insisted that additional research and additional transplants with embryonic pig cells would help reduce the monkeys’ need for insulin injections entirely.

The new research follows hard on the heels of a recent study by the same team of researchers, wherein they showed that transplanted pig pancreatic primordia could cure both type 1 and type 2 diabetes in rats, without using immune suppression drugs.

Scientists across the world have so far tried various types of pancreatic cell transplants in animals and humans with an eye on curing diabetes, but all of them involve anti-rejection drugs. Such drugs have to be taken daily to ward off rejection, and have adverse effects of their own that limit the success of the transplants.

In the current study, the researchers transplanted 19 embryonic pig pancreatic primordial into each monkey, suffering from type 1 diabetes which occurs when islet cells in the pancreas stop producing insulin all together.

Using multiple methods, the researchers determined that the transplanted cells became established within the primates. As the cells matured, they began to release pig insulin, revealed the investigators.

“We found using every method that the cells engraft long-term and, thus, are not rejected by the animals’ immune systems,” Hammerman says.

“It’s been more than two years since our first transplant was carried out. That particular primate doesn’t produce any primate insulin, but has pig insulin circulating in its bloodstream that has reduced by more than 50 percent the amount of injected insulin the animal needs, compared to levels before the transplant. The animals have never received immune suppression drugs,” he adds.

While two of the macaques remain healthy, one became anaemic about six weeks post-transplant, and was euthanized a month later after developing acute respiratory distress.

The researchers could not find a link between this animal’s illness and the pancreatic cell transplants.

One of the two remaining macaques has been followed for 23 months after his first transplant, and the amount of insulin he needs to have injected has declined by some 55 per cent over baseline levels. The other macaque has been followed for 10 months after his initial transplant, and his need for injected insulin continues to decline over time.

“We are encouraged by these results. The absence of a need for immune suppression in diabetic rats gave us hope that we were on the right track. But many findings in rats do not hold true for species that are more closely related to humans, such as non-human primates. This one did,” Hammerman’s colleague Sharon Rogers said.

The researchers will now determine how best to eliminate the need for injected insulin in the diabetic macaques that receive transplants. Their work will demonstrate long-term effectiveness of the technique, and establish the absolute safety of pancreatic primordia transplants.

Hammerman says that his team may conduct clinical trials in humans with diabetes, if their experiments succeed.

“We hope to find out how to apply our findings to human type 1 and type 2 diabetics because the embryonic pig primordia would represent an unlimited source of tissue for transplantation,” he says.

A report on the study, which has appeared online, will be published in the journal Xenotransplantation in November. (ANI)

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