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9/19/2000

Islet Transplants Raise Hope for Diabetes Cure

Kate Traynor

Clinical trials of pancreatic islet transplantation, slated to begin in September, are raising hopes that the procedure will lead to a cure for type 1 diabetes.

The trials are based on Canadian research showing that transplantation of fresh pancreatic islets into patients with type 1 diabetes restores recipients' ability to produce insulin. Except for five brief instances when a patient became ill, none of the seven transplant recipients has required insulin therapy in the year since receiving the islets, according to a report published in the July 27 New England Journal of Medicine but released several weeks earlier by the editors. 

On July 13, President Clinton revealed the identities of 10 centers in the United States, Canada, and Europe, operating under the Immune Tolerance Network (ITN), that will launch a $5 million study designed to confirm the results of the Canadian group. Over the next 18 months, about 40 diabetic patients will receive islet transplants. 

Conducted as an outpatient procedure, transplantation is accomplished by infusing pancreatic islets into the recipient's hepatic portal vein. From that entry point the islets quickly colonize the liver and produce insulin. This method is less invasive than whole-organ transplants, but lifelong immunosuppressive therapy is still likely a necessity. 

Patients in the study adhered to an immunosuppressive regimen that did not include corticosteroids, which can harm pancreatic cells. Instead, transplant candidates received daclizumab---a monoclonal antibody that inhibits T-cell activation—along with sirolimus and tacrolimus. 

Fresh, uncultured islets were used for all the Canadian-conducted transplants. The researchers found that the number of islets needed for insulin independence was about twice that previously reported. Six of the seven patients required islets from two pancreases. The seventh patient, who had a high body-mass index, needed islets from a third pancreas. 

The Canadian research site noted that its protocol involves relatively new immunosuppressive drugs and that wider use could reveal unforeseen adverse effects. Although daclizumab seems to cause few adverse effects, both sirolimus and tacrolimus may affect kidney function. In the study, two patients with pre-existing kidney disease required close monitoring and dosage adjustments after islet transplantation. 

The new multicenter islet transplantation study will be limited to adults with type 1 diabetes. Specific enrollment criteria are listed at the ITN Web site

Even if the new study confirms that islet transplantation works, the procedure's availability depends on the supply of pancreases, which come from cadavers. However, a report in the July 20 issue of Nature raises the possibility that undifferentiated stem cells could someday be used instead of pancreatic islets. 

In this British study, liver tissue samples from nine women who received bone marrow transplants from adult men were tested for the presence of hepatocytes containing the Y-chromosome. The researchers also looked for hepatocytes of male origin in 11 livers that had been transplanted from women into men and later removed. 

In all 20 cases, liver cells containing the Y-chromosome were found. These hepatocytes, according to the researchers, arose from bone marrow stem cells or other stem cells that transplanted with the livers. 

In theory, if stem cells can transform into insulin-producing islets, transplants could be performed using cells cultured in the laboratory instead of islets obtained from donated pancreases, the British researchers suggested. However, a news report in the same issue of Nature noted that stem cells from embryos are more likely than adult stem cells to differentiate into large quantities of insulin-producing cells. 

Until recently, the U.S. government banned the use of federal funds for embryonic cell research. Wednesday, the National Institutes of Health (NIH) announced that it plans to publish in the Aug. 25 Federal Register the final guidelines for research involving human stem cells from embryos. Requests for funding will be accepted after appointment of members to the Human Pluripotent Stem Cell Reviewer Group, which NIH said will occur soon.