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May 9, 2001
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PUBLIC HEALTH
Waiting for the Promised Miracle: Diabetics Look with Hope Toward Islet Cell Transplants
By Leah Shafer
 uring the course of his life, Robert Tesky has probably given himself 40,000 shots of insulin. Diagnosed with type 1 diabetes at age 14, the 54-year-old lawyer from Edmonton, Canada, hadn't experienced many of the complications that often plague diabetics.
But in 1997, Tesky began having uncontrolled low blood sugar and passing out without warning. Being in the right place at the right time, he volunteered in 1999 for an experimental procedure called pancreatic islet cell transplant.
The 1999 procedure has essentially freed Tesky from diabetes.
"It's as close to a cure as you are ever going to get," Tesky says. "It has really given me the life of a normal nondiabetic [person]. I can do what I want, I can eat when I want -- or not eat, as I wish. My blood sugar levels have been almost perfect."
Tesky is one of a few dozen people participating in islet transplant studies in Canada and the United States. Researchers are now taking a closer look at islet transplants; once considered the forefront of innovation, complications and troubles in this area of research have frustrated many.
In the 1970s, the transplantation of islets -- the cells in the pancreas that make insulin -- was hailed as an imminent cure for diabetes. But the procedure turned out to be a big disappointment; the cells were fragile and difficult to harvest, and they died easily in the patient's body. While the cell structure hasn't changed since then, a new protocol for treatment and advances in cell harvesting have increased the procedure's success so much that 40 people are currently participating in a major worldwide research study.
That's great news for the 30,000 cases of type 1 diabetes diagnosed every year in this country. Islet transplants have the potential to normalize blood sugar levels and prevent the dreaded complications of diabetes. If such a transplant had been around when Tesky was diagnosed, at age 14, he might never have known a hypodermic needle or a low-blood-sugar attack.
But there is still a long way to go before the vision of universal treatment is realized, says Daniel Jang, Ph.D., scientific program manager at the Juvenile Diabetes Research Foundation. The islet transplant procedure has been performed successfully on only a few handfuls of diabetics, and the shortage of organ donors is a huge hurdle. But at the same time, the future looks promising for this delicate procedure: Pancreatic islet cell transplants could revolutionize the way we think about and treat diabetes, says Jang.
What's in an islet?
The human pancreas, which is nestled in the abdomen underneath the stomach, harbors about 1 million islet cells. Day and night, these cells pump insulin into the body to keep blood sugar under control.
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Islet transplants have the potential to normalize blood sugar levels and prevent the dreaded complications of diabetes. If such a transplant had been around when Robert Tesky was diagnosed at age 14, he might never have known a hypodermic needle or a low-blood-sugar attack.
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Type 1 diabetes, also called juvenile-onset diabetes, develops when the body's immune system attacks the islet cells and destroys them, leaving the person without a source of insulin.
Islet transplants are simple in theory: Injecting insulin-producing cells into the body of a diabetic creates a new source of insulin. And since we can transplant a whole heart or a liver, it seems like transplanting a few tiny cells shouldn't be too difficult.
But the reality is far from simple.
Lingering obstacles
The fragile nature of islet cells means that a significant number of them will die while being harvested, and even more will perish once injected into a patient. There's also a good chance that a patient's body will reject the foreign cells.
One solution is to improve the isolation of human islets so that the cells are more likely to survive the harvesting process and more efficient in their release of insulin, explains Jeffrey L. Platt, M.D., professor of surgery, immunology, and pediatrics at the Mayo Clinic.
To survive the patient's immune system -- which, as Dr. Platt points out, sees the new islets as foreign invaders -- doctors have begun "packaging" the islets in synthetic materials, either individually or in clusters. The openings in these packages are large enough to allow molecules such as glucose, oxygen, and insulin in and out, but are to too small for components of the immune system, like antibodies and lymphocytes, to reach the islets and destroy them.
In a paradoxical twist, the same immunosuppressant drugs traditionally used to keep the body from rejecting the islets cause a host of side effects, one of them being a reduced ability to absorb insulin, the very thing the islets are producing. At the Auckland School of Medicine, in New Zealand, researchers led by Robert Elliott, M.D., have managed to transplant islets into patients without the use of immunosuppressives, which are toxic. This alone is a great achievement, but the source of Dr. Elliott's islets also heralds a breakthrough: The cells came from pigs.
Bringing home the bacon
Pigs are one promising answer to the problem of islet cell shortages -- they're quickly bred and readily available. These are not the same pigs that are the source of the bacon found in your grocery store; the animals that yield islets are porcine perfection -- pigs bred for generations to express both human and pig proteins in their cells. This breeding lessens the chance of rejection by the human body.
Xenotransplantation -- the implementation of living cells from other species when human donors are not available -- is relevant to the islet field. As Dr. Platt points out, "While the transplantation of human islets is an exciting advance, it can only scratch the surface of need because diabetes is such a widespread disease and organ donors are relatively scarce."
People often worry about using animal parts for humans because we've seen pathogens -- especially viruses -- jump from species to species. There's no guarantee that this wouldn't happen, but the pigs used for islet cell harvesting are bred for generations to be pathogen-free and are often extensively tested for known viruses, even those that have not begun replicating.
Just around the corner?
The headline "Just Around the Corner," from a medical publication in the early 1970s, proclaimed that islets would soon offer a cure for diabetes. But the fragile little cells have foiled researchers time and time again, and what seemed like a quick solution 25 years ago has turned into a logistical nightmare. Since diabetic rats and mice were successfully treated with islet transplants in the early 1970s, the progress of science has been frustratingly slow.
But successes like that of Robert Tesky make the trouble worthwhile. He's living a life he never dreamed possible, and his islets are still performing at full capacity. For the procedure to become widespread, Tesky sees two main obstacles. "They should find a way to do this without anti-rejection drugs because there's a trade-off when you have a procedure like this. You're trading the risks that come with insulin dependency for the risks that come with long-term use of anti-rejection drugs," he says.
"Also," explains Tesky, "they need to find an alternate or artificial source of islets. If that problem can't be solved, they'll never be able to make a significant dent in the number if insulin-dependent diabetics because there are so many of them and so few organ donors."
Researchers are facing these two hurdles now, and the future looks promising for the many insulin-dependent diabetics who rely on daily injections. Islet therapy won't come overnight, but it promises to be worth the wait.
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