Cell Transplants Can Cure Diabetes, But Drawbacks Abound

Type 1 diabetes afflicts more than one million Americans. It is the most severe form of the disease, in which the body's immune system attacks insulin-producing cells required to keep blood sugar at normal levels. Extremely low blood sugar can result in seizures, impaired cognition, or unconsciousness and in the most severe diabetics the complications are not well controlled by insulin.

Replacing insulin-producing cells in the pancreas can free diabetics from lifelong insulin injections and effectively cure the disease. The transplantation of these "islet" cells can now be done in two ways, through a whole pancreas transplant or through a less invasive and less costly process of injecting just the islet cells.

While the cell-only method had been hailed early on as an important advance in treating Type 1 diabetes in particular, there are many drawbacks. After three years, cell transplants appear to work in only half the patients, it takes more than one donor pancreas to produce enough pure islet cells for the multiple injections required, and many patients face a trade-off between insulin injections and lifelong use of toxic immunosuppressant drugs used to keep the body from rejecting the new cells.

"Diabetics, it's thought, don't have any or have very few islet cells," said Soumitra Ghosh, PhD, Medical College of Wisconsin Associate Professor of Pediatrics (Endocrinology). "They're being destroyed by the body's immune system, so the idea is to replace them. In islet transplantation you take islet cells from cadavers and inject these cells back into a diabetic.

"We give immunosuppression because these are foreign cells from a different person. To protect these cells from being rejected, you have to give some level of immunosuppressant drugs. That's why it works, because you've got functioning islets that are working in another body whose immune system has been curtailed to a certain extent."

Insulin-Free, at a Cost
Dr. Ghosh conducts research into genetic causes of diabetes at the Max McGee Center for Juvenile Diabetes at Children's Hospital of Wisconsin. That work may be the way of the future in treating diabetes by addressing the disease at the most basic level, the genes, but he sees some short-term promise in islet cell transplants.

"That's the great breakthrough that came in the year 2000," said Dr. Ghosh. "Research indicates that about half of the people who received islet transplants several years ago are insulin-free. That had never happened before. That's the big thing that's exciting a lot of people, but the literature also talks about the related issues and challenges because it's not as easy or dramatic as the initial results suggested. Because, if you wait long enough, a lot of these patients are going back to insulin."

"The most likely candidates for islet transplants at the moment are the very severe diabetics, the 'brittle' diabetics whose control of their diabetes is very, very difficult even with the maximum amount of insulin," said Dr. Ghosh. "They're still not able to keep blood sugars low or within the normal range."

Donor Availability an Issue
According to the Juvenile Diabetes Research Foundation International, there are about 30,000 new cases of Type 1 diabetes in the US each year but only about 3,500 donor pancreases usable for producing islet cells.

"One of the main issues in islet transplantation is the available number of cadaver cell donors," said Dr. Ghosh. "That's the huge limitation. The islet isolation procedures are fairly good, so that's been worked out, but it's really the number of donors and the immunosuppression at the end. Can we get enough islet cells, and if we can, can we not harm the patient significantly through immunosuppression such that they are able to survive and lead a relatively normal life with reasonable blood sugar levels?"

The immunosuppression issues are a major reason why islet transplants are not viewed as an effective cure for children with diabetes. The anti-rejection drugs suppress the immune system to the degree that it becomes less effective at fighting infection and warding off cancer.

"Some researchers say that islet transplantation may not be worth it," said Dr. Ghosh. "Like everyone else in the field, I'm hopeful for this mode of therapy. But it may be one of these things that has a lot of support and is very exciting at the beginning, but with time the results show that people are back to square one."

Whole Pancreas Transplants
According to one Medical College physician, using whole pancreas transplants to cure diabetes may ultimately be more efficient even though the procedure is more invasive and costly.

"There are really two ways that surgeons can cure diabetes," said Allan M. Roza, MD, Medical College Professor of Transplant Surgery. "One is transplanting the whole pancreas, and the other is removing the cells that produce insulin from the pancreas and transplanting those. When either procedure is successful, the results are the same. Namely, the patient comes off insulin.

"So the benefits are many. They include freedom from insulin, and also the impact is probably most profound on the so-called 'secondary' complications of diabetes. These include kidney failure, nerve damage, blindness, and hardening of the arteries. Having these cells in place in one of the two ways that we can do it will normalize blood sugar, give the patient back insulin, and slow down, prevent, or even reverse secondary complications.

"An advantage of transplanting the whole pancreas is that most patients who get a pancreas transplant also come to us in kidney failure. So they need both, a kidney and a pancreas. We're now so successful in preventing rejection that a patient who is diabetic will not lose the kidney from rejection, but they might lose the kidney from the diabetes all over again. So having a pancreas in place is also protective if the individual gets a new kidney. That's a significant advantage in this era where there are more patients needing kidney transplants but there aren't enough organs to go around."

Islet Transplants are Technically Difficult
There is currently no islet transplant program at Froedtert & Medical College, Dr. Roza said. "The islet transplant is a very technically difficult procedure to do. Even in the best hands, it works about half the time. Most patients need multiple injections of islets; in other words, the islets you get from one pancreas are probably not enough.

"You may be talking about four pancreases that are being used to cure one patient in islet transplantation, whereas with the whole pancreas transplant you're seeing one pancreas cure one patient. In terms of utilization of organs, whole pancreas is much more efficient.

"We were interested a few years ago in developing islet transplants, and we went into this knowing that there were difficulties. If I could predict five years into the future, we'll probably have five or six centers of excellence in the country that will continue to do islet transplants. Then, for example, we would find an organ donor here, send them the pancreas, they would isolate the islets and then we would transplant them.

"Certainly, whole pancreas transplant is a wonderful therapy. When islets work, it's wonderful. But cell transplant is still a transplant and you need anti-rejection therapy. But it does allow us to use as many organs as possible, such as in a case where we have a pancreas from a donor that can't be used whole for various reasons, sometimes those are good pancreases for islets. It can improve the utilization of precious organs.

"It will never equal whole pancreas transplant in terms of the number of patients it affects, but if we can transplant a hundred patients nationwide a year - even if in a perfect world we'd be doing thousands - the more patients who get the benefit of this therapy either through whole pancreas or islet transplants, we're helping."

Dan Ullrich
HealthLink Contributing Writer

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.