Now That Islet Transplants are All the Rage What are the Next Steps?

When Dr. James Shapiro sees teaspoons of freshly harvested islets floating in a fluid matrix at the bottom of a test tube, he sees “the difference between someone having diabetes—or not.”

Shapiro, who is the leader of the landmark Edmonton Protocol, was among six top scientists in islet research to discuss the latest transplantation issues during the October 28, 2000 World of Hope Conference in New York City. About 320 people attended the Diabetes Research Institute-sponsored event, which focused on “Islet Cell Transplantation: What Are the Next Steps?”

Islets-Strides Toward a Cure

The Edmonton Protocol proved islet transplantation works with the use of anti-rejection drugs. Therefore, the eyes of the diabetes community are turned toward transplanted islets as a potential diabetes cure.

Success of islet transplantation as a cure for diabetes hinges on solving two problems: finding an adequate supply of islets, and eliminating the need for anti-rejection drugs.

“[The need for anti-rejection drugs] severely limits our ability to market this solution to children,” says Camillo Ricordi, MD, scientific director at the Diabetes Research Institute of the University of Miami. This is because anti-rejection drugs are still not perfected for safe use over extended time, i.e., when used from childhood.

A Simple Procedure

For those who have had islet transplants, the procedure is a simple one.

“The transplant is a drive-through procedure,” Ricordi explains. “Three quarters of our patients go home in less than a day. Whereas, if you do a pancreas-transplant procedure, patients can end up back in the hospital for a number of weeks and even months.”

Ricordi says the actual transplant, called intraportal islet infusion, is “as easy as a blood transfusion.” The cells are injected into the main vein to the liver of the conscious patient. Only local anesthesia is used.

“This is not even a surgical procedure,” he says. “The patient is awake and talking to us during the short procedure.”

The Major Problem

Ricordi adds that transplanting islets offers a “paradox” because they are very sensitive cells that still require the protection of anti-rejection drugs.

“Transplants require an estimated 2 1/2 times the amount of islets you would have without anti-rejection drugs,” says Ricordi. “It takes islets from two pancreases to treat one person’s diabetes. With this ratio, we can treat just a small fraction of the diabetic population.”

Ricordi says even if transplant surgeons do one pancreas to four patients, they would still be behind.

Working to Improve Drugs and Technology and Make Transplants Affordable

Researchers are working to develop better anti-rejection drugs that are less harmful to the patient. Improving the drugs would reduce the number of transplanted cells that are destroyed, and consequently fewer cells would be needed for the procedure. In addition, there are 10 centers funded by the National Institutes of Health, nationwide, working to improve islet-transplant technology.

“The strategy now is to get together with all the centers and deliver ways to generate beta cells from stem cells,” Ricordi says.

Strategies funded by NIH are also focused on:

Restoration of T-cell function to eliminate autoimmunity when the body destroys its own insulin-producing cells. If communication with T-cells is blocked, the body would be less likely to reject the transplanted cells through autoimmune destruction, as it does with cells at the onset of diabetes. In mice these studies have been successful. With just a few days of anti-rejection drugs they accept the cells. But studies continue (in larger animal models to increase transplant tolerance and eliminate need for lifelong immuno-suppressants), said Norma Kenyon, Ph.D., the director of pre-clinical islet transplantation at DRI.

In-vivo beta cell proliferation from stem cells.

The 10 NIH-funded diabetes research centers working on islet experiments in 2001 are scheduled to do four transplants each, for a total of 40 patient trials during the year in the $144 million project.

“This could put a cure within our reach by proving the technology’s success in repeated trials,” says Shapiro, whose department gets 100 requests per day for the procedure.

If islet transplants are to eventually help any people with diabetes, it is likely additional research will have to occur in making them affordable.

Edmonton-style anti-rejection drugs tallied a $57,000 bill per patient for the first year, says Ricordi. And the cost of the actual procedure is rather expensive. At $100,000, the islet transplant costs the same as a pancreas transplant.

“We’re in a stage where this procedure is in very few cases and is therefore very expensive,” Ricordi said.

Other Studies in Islet Grafting

Kenyon, who is also associate director of the DRI cell transplant center, has reached a major breakthrough by reversing diabetes in non-human primates. She worked to block communication between islets and T-cells to prevent graft rejection. By increasing transplant tolerance in Rhesus monkeys, Kenyon reduced the need for lifelong anti-rejection drugs.

“Not only did the islets survive in the liver,” she says, “But they continued to improve over time as they established new connections, blood vessels and cell-level communications within the liver.”

Continuing research, like that presented by Kenyon, Shapiro, Ricordi, Inverardi, Kevan Herold and Robin Nemery at the DRI World of Hope Conference 2000, is bringing islet-transplant technology closer to becoming a viable cure for diabetes. Through the scientists’ presentations and panel discussion, hundreds of people in the diabetes community gathered a deeper understanding for the future of islet cells technology.

“We have a firm belief that the only way a cure will come about is by the exchange of information,” said Tom Karlya, director of development for DRI. “As the parent of a 10-year-old with diabetes, I felt the strength of so many in one room.”

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