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Islet Cell Transplant Research Explained
Amir Hanna MB, BCH, FRCPC
“I feel like I’m free. It’s a miracle.”
“It’s like getting a Christmas present.”
These two statements, cited in a Toronto Star article of June 27, 2000, give the reactions of two of the participants in the islet transplant research project conducted at the University of Alberta. This research, undertaken by a team led by Dr. James Shapiro, has stimulated excitement around the world. Diabetes Dialogue readers will have some familiarity with islet transplants, as a description of the process and its potential was outlined in an article in the Winter 1999 issue, authored by Dr. James Shapiro and Dr. John Elliott. However, given the importance of the research to persons with diabetes, a brief recap is in order.
What Are Islet Cells?
In a healthy pancreas, there are two different kinds of cells: one kind secretes digestive juices into the bowel to digest different food ingredients, and the other kind secretes hormones like insulin and glucagon into the blood. The latter cells are grouped in small islands in the pancreas; they are called the Islets of Langerhans. Each of these islets contains a few thousand cells, and a total of one to two million insulin-secreting cells. In a person with type 1 diabetes, the insulin producing cells are attacked by the immune system and are destroyed, leading to a deficiency of insulin and high blood sugar. For the person with diabetes to survive, insulin has to either be provided by injections or, as this research shows, the islet cells can be transplanted to provide insulin.
Background to the Research
Researchers had tried for more than 20 years to successfully transplant the cells that produce insulin from a healthy pancreas into the body of a person with diabetes. Yet of 405 attempts since 1970, 92 per cent of the recipients were back on insulin within a year. “People didn’t believe it would work,” said Dr. Shapiro to Canadian Press reporter Bob Weber, in a June 8, 2000 article in the Saskatoon Star Phoenix. Dr. Shapiro had, in fact, gone on to other work, performing pancreas transplants in Baltimore, Maryland.
Following a call from the University of Alberta, however, he decided on one more try, using a new approach. As Dr. Shapiro stated to Weber, “It was a rainy day in Baltimore, and I was sitting in my room waiting for a pancreas operation. I sat down and wrote what evolved into the Edmonton protocol.”
The Edmonton Protocol
Islet cells are transplanted directly from a donor pancreas after isolation and purification, without prior storage. Because the islets are considered foreign to the host, drugs have to be used to prevent the body from rejecting the cells. Three new anti-rejection drugs were used in this protocol. The combination did not contain cortisone-like drugs known to have many side effects, and that have a tendency to raise blood sugar levels. Besides preventing the rejection of the transplanted islets, these new drugs also prevent the possible attack of the immune system on the cells, a process that by itself may recreate type 1 diabetes. The transplant procedure involves injecting the islets through a catheter introduced through the skin to the liver, then to a large vein returning blood from the abdomen to the liver. The cells settle in the liver, and even though they are in a different organ, the cells take root. They then produce insulin and almost-perfect control of blood sugar.
Early Results
Of the seven transplants done by Dr. Shapiro’s University of Alberta team in the past year, none has failed. His work was published in the prestigious New England Journal of Medicine, July 27, 2000. All the patients have been able to stop injecting insulin, and remained with almost normal blood glucose. As Dr. Shapiro and his team note in a report of their findings, “Pancreatic transplantation provides excellent glycemic control, and although the outcome of the procedure has improved dramatically over the past decade, it remains an invasive procedure with a substantial risk of morbidity. Our findings indicate that islet transplantation is associated with minimal risk and results in good metabolic control, with normalization of glycosylated hemoglobin values and sustained freedom from the need of exogenous insulin.”
Much Still To Be Done
In an interview in the Toronto Star, May 25, 2000, Dr. Shapiro’s team stressed that it will be some time before the majority of the world’s 130 million people with diabetes can reap the benefits of the research. Further testing on a larger scale will be necessary. Moreover, possible side effects of the autoimmune drugs used will require close monitoring. The procedure itself still has to go through lengthy trials. The challenge ahead lies in getting enough organs for transplant purposes. Yet, in Canada, with its low donation rates, scientists must turn to research to get the needed supply. That research will continue. In this regard, Dr. Shapiro will be the lead investigator in a new eight-centre international trial to determine whether the Edmonton protocol can be duplicated. If these trials are successful, and problems such as islet availability are overcome, then indeed a miracle will have occurred. This will be in the future, and while caution is the watchword for now, that future is a great deal brighter than before.