Island cell transplantation, an experimental pancreatic procedure, may relieve some diabetics of the need for insulin injections, but it is not easy, so other islet cell replacement techniques are being investigated.
The islets of Langerhans, or “islet beta cells” (as they are more commonly called), are the natural reservoir of insulin-producing cells in the body.
It is these cells that are destroyed or severely damaged in type 1 diabetes and are lacking in some type 2 diabetes. Because of the lack of a natural source of insulin, the hormone that controls blood sugar, people with type 1 diabetes must take daily injections of insulin.
But for the past decade, researchers have been studying and fine-tuning techniques to find replacement islet cells with the goal of restoring natural insulin production and release and relieving the need for insulin injections in people with type 1 diabetes. This treatment generally has little efficacy in patients with type 2 diabetes caused by a different disease process.
One proven method of islet cell transplantation is pancreas transplantation, a large gland at the back of the stomach where the islet β cells accumulate. Studies have shown that over a period of at least 5 years, about half of patients have been relieved of the need for insulin injections through pancreas transplantation.
However, because of the risks of transplantation and the need to take anti-rejection medications after transplantation, this procedure is primarily an option for those who have received a kidney transplant due to end-stage renal disease. According to the American Diabetes Association (ADA), simultaneous kidney and pancreas transplantation in selected patients does not increase risk, may improve survival of the transplanted kidney, and will restore normal control of blood glucose.
However, the ADA diabetes guidelines also state that pancreas transplantation has been only partially successful in reversing some of the serious long-term side effects of diabetes. Pancreas transplantation does reverse kidney problems and the need for multiple daily or sometimes multiple insulin injections, but chronic conditions like eye disease and neurological abnormalities remain a problem for these transplant patients.
Islet cell transplantation
Islet cell transplantation is a minimally invasive alternative to pancreatic transplantation. In this experimental procedure, islet β-cells are identified, isolated, and removed from the donor pancreas and then injected into a major vein connected to the liver. After injection, the islet cells enter the microvasculature, where they are surrounded and immobilized by liver tissue. In this way, the cells control the production and secretion of insulin, effectively turning the liver into a replacement for the pancreas.
One problem with this approach is that human islet β-cells are rare and difficult to detect; they actually make up only 1% of all cells in the pancreas (most of the remaining cells produce and secrete enzymes that aid in digestion). In addition, some islet cells are inevitably destroyed during the excision process, said one diabetes researcher.
“Cutting up the pancreas, isolating the cells, and then transplanting them, all in one day is tough, especially when you also consider that it may take a whole day to try to isolate the cells but end up not getting enough of them.” said Emmanuel Opara, PhD, associate professor in the Department of Experimental Surgery and assistant professor in the Department of Cell Biology at Duke University Medical Center in Durham, N.C., USA.
Opara and his colleagues are looking for ways to replace human islet cells, including using islets taken from the pancreas of pigs. Although the use of animal organs in humans is controversial, insulin derived from pig and bovine pancreases has been used since the early 1920s, when commercial insulin production began; the use of human insulin is a relatively recent development.
Pig islet cells are very similar in nature and function to human islets, but because they come from animals, they are considered foreign invaders by the patient’s immune system, which has specialized cells to hunt down, label, and kill them.
To address this problem, Opara and colleagues at Duke University developed a special delivery sphere that consists of a complex carbohydrate called alginate. These spheres surround, or “encase,” the islet cells, and are reportedly porous enough to allow blood sugar to enter and insulin to exit, while protecting the islet cells from the immune system. These spheres are a bit like the battlements used by archers to defend ancient castles.
Researchers at Duke University are also working on a method to freeze-cut islet cells. “One of the things I’ve been doing is looking for ways to store these cells in a viable state. That way when the need arises, it’s similar to going to the doctor and getting a prescription (for islet cells) and then going to the pharmacy and picking up the medicine.” Opara describes.
In addition to building islet cell reserve mechanisms, the benefit of this technology is that it diminishes the aggressiveness of these cells to the immune system, so they can survive longer when transplanted into people with type 1 diabetes, Opara said.
Island slices, viruses, and stem cells
Other research teams are working on an islet cell sheet surrounded by porous plastic, a synthetic sheet that could theoretically serve as a bioartificial pancreas. Still other researchers are experimenting with viruses, trying to make the immune system more receptive to islet beta-cell transplants in the form of a biological “stealth” technology.
As WebMD reported in 2001, researchers at the National Institutes of Health are working to develop a new way to restore insulin production by inducing embryonic stem cells to become specific insulin-producing cells like islet β cells. If the technique works in humans, it could mean a major breakthrough in diabetes treatment, even replacing insulin injections, the researchers report in the April 26, 2004, issue of Science.
But because the emerging insulin-secreting cells are derived from a non-specialized cell found only at an early stage of embryonic development, they would face strong political and religious opposition to the use of human embryonic cells for medical research in the treatment of human disease.