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Islet Transplants Making Progress
In the late 1960s scientists started toying with the idea of replacing insulin producing cells (islets) to cure diabetes. These islets make up a mere one to two percent portion of the pancreas. The goal of this work is that eventually, one dose of insulin producing cells could last a lifetime and not require drugs to suppress the immune system.
In 1990 an automated method was perfected for the retrieval of enough islets from a single pancreas to reverse diabetes. This method is now used to obtain islets from both human and animal pancreases.
Avoiding Rejection
Currently, immunosuppressants must be taken for life after an islet transplant. They weaken the immune system making the body susceptible to infection, cancer and many other sicknesses. One of today's major challenges is to find a way to prevent the body's immune system from rejecting the foreign islets without the use of immunosuppressants.
Jeffrey Platt, MD, has devoted a considerable amount of his time to overcoming the immune system barrier in his research.
"This has occupied the majority of efforts in my lab," says Platt. "As well as, will the animal islets really work well enough to justify a transplant?"
Doctors are attempting to fool the immune system and protect the islets from being attacked by the recipient's immune system by encasing them in a protective shell. There are two separate strategies, microencapsulation and macro-encapsulation. Macro-encapsulation is the encapsulation of islets together as a whole. Micro-encapsulation is when each islet is individually encapsulated.
Robert Elliott, MD, from the Auckland University Medical School in New Zealand, is working with individually encapsulated pig islets that are encased in a glue-like coating made of seaweed and hardened with a calcium solution. They are then inserted into the recipient's abdominal cavity. Elliott says the procedure will ultimately be quick and effective.
"It is likely that a day's stay procedure would be developed," he says.
In May 1996, Elliott's lab, Diatranz, conducted two transplants in cooperation with VivoRx and Patrick Soon-Shiong, MD. The two research labs combined technologies, using VivoRx's encapsulation and Elliott's pig cell preparation. Elliott was encouraged by the results.
"Peak production of pig insulin (about one-third of the daily insulin requirement) occurred between three to six months post transplant and has slowly dwindled since then," says Elliott.
After two years, the patient who was on immunosuppressants prior to the transplant is producing no more insulin. The other patient is not on immunosuppressants and is producing about 10 to 15 percent of his daily insulin.
"It was clinically useful when the peak production was resulting in a major insulin dose reduction and an absence of hypos and so forth," adds Elliott. "If we could remove the need for insulin for even one to two years, or even reduce the dose of insulin with improved blood sugar control, it would be worth doing multiple transplants over time."
Pig Islets Injected
Another method involves pig islets being injected into the portal vein which leads to the liver. A procedure which can be done in a doctor's office under local anesthetic. The islets are not introduced into the pancreas because the procedure would then require surgery and the immune system would likely re-attack the islet cells. The extreme fragility of the pancreas also prohibits introducing new islets to the pancreas.
Using this injection method, Drs. Ricordi, Alejandro, Mintz and Tzakis at the Diabetes Research Institute in Miami, Florida reported success using pig islets. Of the three patients who underwent transplantation in 1990, two maintained long-term islet function for seven years and one patient was free from insulin injections for five years.
Challenges for the Future
Even in the face of these successes, Platt notes three major hurdles that must be overcome before islet cell transplantation can be a serious contender as a cure for diabetes.
- Islets must overcome the immunological reaction.
- The islets must survive and produce insulin ideally for the lifetime of the recipient.
- Islets from other species could pass infectious agents on to humans.
However, Alastair Gordon says funding is an even more pressing issue. As a result, he has started a fundraising organization called the Islet Foundation which can be reached on the Internet at www.islet.org or by telephone at (416) 486-8784.
Emmanuel Opara, PhD, at Duke University agrees that money is the greatest hurdle. "We'd like to proceed with clinical trials on baboons, but it will cost about one million dollars," says Opara who is currently exploring several avenues of fundraising from philanthropists to grant writing.
And when will islet cell transplantation successfully reverse diabetes?
As of yet, no one can say.
"If researchers have a reliable source of funding, the best and most promising will become clearly evident," says Gordon, who hopes that islet cell tranplantation will become the cure he has been waiting for. "If so, I wouldn't hesitate to have it done."
Categories: Blood Sugar, Diabetes, Insulin, Islet & Pancreas Transplant
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