Islet Cell Transplant: Still Promising?
By Neil Osterweil
Reviewed By Charlotte Grayson
Although the name may conjure images of wind-swept outcroppings off the northern coast of Scotland, the islets of Langerhans, or "beta-islet cells of the pancreas" as they are more commonly called, are the body's natural store of insulin-secreting cells.
It is these cells that are destroyed or severely damaged in type 1 diabetes and deficient in some cases of type 2 diabetes. Lacking a natural source of insulin, a hormone essential for controlling blood sugar, people with type 1 diabetes must take daily insulin injections.
But throughout the last decade, researchers have been investigating and fine-tuning techniques for replacing beta islet cells, with the goal of restoring natural insulin production and release and eliminating the need for insulin injections in people with type 1 diabetes. People with type 2 diabetes, which is caused by a different disease process, would generally not benefit from this type of therapy.
One proven method of islet-cell transfer is through transplantation of the pancreas, the large gland (located behind the stomach) where beta-islet cells live. Studies have shown that pancreas transplantation can eliminate the need for injected insulin in approximately half of all cases for at least five years.
Yet because of the risks of transplant surgery and the necessity for taking anti-rejection drugs after the transplant, this procedure is primarily an option for patients who are also receiving kidney transplants due to advanced kidney disease. According to the American Diabetes Association (ADA), simultaneous kidney and pancreas transplants in select patients do not increase the risk for the patient, may improve survival of the transplanted kidneys, and will restore normal control of blood sugar.
The ADA diabetes guidelines also note, however, that pancreas transplantation is only partially successful at reversing some of the serious long-term side effects of diabetes. The procedure does reverse kidney problems and the need for daily and sometime multiple injections of insulin. But chronic conditions like eye disease and nerve abnormalities frequently continue to be a problem in these transplant patients.
At the time this article was written, there were 1,389 people on the national waiting list for a pancreas transplant, and an additional 2,409 people waiting for a combined kidney and pancreas transplant, according to the United Network for Organ Sharing (UNOS).
A slightly less invasive alternative to pancreas transplantation is islet-cell transplantation alone. In this experimental procedure, beta-islet cells are identified, isolated, and removed from donor pancreases and are injected into a major vein connected to the liver. The injected islets find their way into microscopic blood vessels and become surrounded and fixed in place by liver tissue. Once there, the cells take over insulin production and secretion, effectively turning the liver into a substitute pancreas.
One problem with this approach is that human beta-islets are few and hard to find; they actually comprise only 1% of all cells in the pancreas (most of the remaining cells produce and secrete enzymes that aid in digestion). In addition some of the islets are inevitably damaged or destroyed during the harvesting process, explains a diabetes researcher in an interview with WebMD.
"The process of harvesting the pancreas, isolating the cells, and then transplanting them all in one day is pretty tough, especially when you also take into account the situation that you might actually spend that entire day trying to isolate cells and never come up with enough cells from that procedure," says Emmanuel Opara, PhD, associate research professor in the department of experimental surgery and assistant research professor in the department of cell biology at Duke University Medical Center in Durham, North Carolina.
Opara and colleagues are looking at alternatives to human islet cells, including the use of islets taken from pig pancreases. Although the use of animal organs in humans is controversial, insulin derived from pig and cow pancreases has been in use 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 an animal they are seen as foreign invaders by the patient's immune system, which sends out specialized cells to hunt them down, tag them for removal, and kill them.
To get around this problem, Opara and colleagues at Duke have developed special drug-delivery spheres made up of a complex carbohydrate called alginate. The spheres surround, or "encapsulate" the islet cells, and are reported to be porous enough to let blood sugar come in and insulin go out while protecting the islet cells from immune-system act. The spheres are a little like the arrow slits used by archers defending ancient castles.
The Duke researchers are also investigating methods for freezing harvested islet cells. "One of the things I've been doing is to design procedures that will enable us to store these cells in a very viable state, so that when you require them you will approximate the situation of going to a doctor to get a prescription [for islet cells] and then going to the pharmacy to pick them up," Opara tells WebMD.
In addition to building islet-cell reserves, the technique has the beneficial side effect of making the cells less offensive to the immune system, thereby helping them to survive longer when transplanted into a patient with type 1 diabetes, Opara says.
Islet Sheets, Viruses, and Stem Cells
Other research teams are working on sheets of islet cells that are surrounded by a porous plastic; the resulting sheets could theoretically act as bio-artificial pancreases. Still others are experimenting with viruses that could make beta-islet cell transplants more acceptable to the immune system, in a form of biological "stealth" technology.
And as reported by WebMD in 2001, researchers at the National Institutes of Health are working to develop a new method for restoring insulin production by coaxing embryonic stem cells into becoming beta-islet cells specialized type of insulin-producing cell. If the technique works in humans, it could represent a major breakthrough in the treatment of diabetes and could even replace injected insulin, report researchers in the April 26 issue of the journal Science.
But because the newly minted insulin-secreting cells are derived from a type of non-specialized cell found only in the earliest stages of embryonic development, a human version of the treatment would face stiff opposition from the political and religious right, who oppose medical research using cells derived from human embryos.
In 2001, the Bush administration announced a ban on research using cells derived from newly-created embryos (such as those discarded daily by fertility clinics), restricting scientists to working with currently available stem-cell lines; stem cell researchers said the decision cripples their ability to do meaningful research, and could delay the development of life-saving treatments -- like those for diabetes -- by years or even decades.
Originally published March 17, 2003.
Medically updated June 18, 2004.
SOURCES: American Diabetes Association. United Network for Organ Sharing. Emmanuel Opara, PhD, departments of experimental surgery and cell biology, Duke University Medical Center, Durham, N.C. Diabetes Care, January 2003. Science, April 26, 2001. WebMD Medical News: " Stem Cells Turned Into Insulin Producers Offer Promise for Diabetics." Islet Sheet Medical, San Francisco.
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