Local researchers, including those from the Northwest Tissue Services, will take another major step toward an eventual cure for Type 1 diabetes when they begin conducting a phase I clinical trial sometime this summer. The experimental treatment will involve the isolation of insulin-producing islet cells from cadaveric donors and transplantation of the islets into 12 to 14 seriously ill diabetes patients.

The Northwest Tissue Services will play a critical role: that of recovering pancreatic islets and processing them for transplant.

A bulb-tipped needle is used to insert enzymes into the pancreatic duct. The enzymes break down surrounding tissue in order to liberate the islets.

Participation in two clinical trials
In 1999, the Tissue Services was among six local institutions awarded a three-year grant by the Juvenile Diabetes Research Foundation. Headed by Paul Robertson, M.D., director of the Pacific Northwest Research Institute, the consortium includes the University of Washington, Virginia Mason Research Center, Swedish Medical Center, and the Fred Hutchinson Cancer Research Center, as well as the Northwest Tissue Services. This consortium is known as HITS, for Human Islet Transplantation in Seattle. The initial project goal was to transplant islets into seriously ill Type 1 diabetics who were also receiving kidney transplants.

However, with last year’s news of the islet-only transplant success in Edmonton at the University of Alberta — seven of seven Type 1 diabetics were cured — the world focus in islet research changed. In July, the Immune Tolerance Network (ITN) and the National Institutes of Health (NIH) funded 10 programs to duplicate Edmonton’s success. The Tissue Services’s was among them.

“Our efforts are now also focused on the Edmonton protocol,” says islet program scientific director, Jo Anna Reems, Ph.D. “Consequently, we are preparing to transplant islets under two protocols. The first is to reproduce the islet-only transplants by adopting the methodologies required by the ITN. A site inspection is also needed. The second is the kidney-islet protocol, which requires an investigational new drug (IND) submission.” FDA approval is expected soon.

The other pending issue is the modification of a COBE cell processor by retrofitting it with a critical refrigeration function in order to duplicate the original Edmonton protocol and provide a high yield of quality islets.

Processing, transplanting the islets
Found in the pancreas, islets are clusters of insulin-producing cells called beta cells and others that produce enzymes to aid digestion. Healthy beta cells release insulin to help maintain normal glucose levels in the body. In Type I diabetics, these insulin-producing cells are destroyed by the body’s own immune system. Much of the recent success of the Edmonton protocol is attributable to the elimination of steroids, which were used in previous islet transplants.

Each transplant recipient needs about 500,000 islets. Within 12 hours of removal, the pancreas is washed in decontaminating solutions and infused with a digesting enzyme, which gradually dissolves most of the pancreatic tissue except for the islets. The COBE cell processor is then used to isolate the islets. Transplantation must occur within two to four hours after isolation.

Islets will be transplanted into the recipient’s liver. Using a needle guided by ultrasound technology, doctors at Virginia Mason Medical Center, Swedish Medical Center and the University of Washington will insert the islets into the portal vein, the liver’s major blood vessel. Within days, the islets should begin producing insulin at the desired levels.

Looking ahead
The Tissue Services has processed more than 100 pancreata to prepare for islet transplants. The HITS islet-kidney regimen is coordinated by Dr. Christopher Marsh, associate professor of surgery at the University of Washington, where the first such transplant will take place. The first transplant in the ITN / Edmonton trial will occur at Virginia Mason Medical Center.