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Take Note: You Better Know Your Islets

Sep 1, 1995

Research Update

It seems like fantasy, something the doctors on Star Trek would have in their repertoire. But this is not science fiction-as we hurtle toward the 21st century, researchers are racing toward a practical method of islet transplantation, the procedure that could revolutionize diabetes treatment.

In fact, successful islet transplantation would cure diabetes. Because if doctors are able to place healthy, insulin-producing islets into a person with diabetes, in a minimally invasive procedure that needs to be repeated only occasionally, diabetes care as we know it would be finished. Patients might occasionally need insulin, and would of course want to keep an eye on their blood glucose levels, but the often grueling regimen many of us now follow would be a thing of the past.

What exactly is islet transplantation, anyway? In fact, what are islets?

What Are Islets?

Technically, they're called the islets of Langerhans. These are clusters of cells that lie within the pancreas and produce insulin, glucagon and other hormones. When a person lacks beta cells, he or she also lacks a sufficient supply of these vital hormones, resulting in the condition we call diabetes. Islets have been said to resemble fine golden sand, measuring about 1/4 millimeter in diameter-visible to the naked eye. Scientists can isolate islets from pancreatic tissue only with much effort. If islets can be likened to sand, the pancreas can be compared to a bologna sandwich-try getting sand out of your sandwich once you've dropped it on the beach.

The current method of isolating islets involves disintegrating the pancreatic tissue with enzymes, leaving behind the islets which are slightly heavier than common pancreatic cells. Unfortunately, this procedure costs up to $8000 and many of the islets are routinely lost in the process. The average islet recipient requires 10,000-20,000 islets per kilogram of body mass. To put this into perspective, an average-sized man would need islets from approximately two to eight donor pancreases to complete his transplant.

The islets come from the pancreases of cadavers, but only a few thousand of these become available each year, since most people don't become donors. Even if islet transplantation were perfected, there are 2.3 million insulin users in the United States, which means that there just wouldn't be enough islets to go around. We can get insulin from pigs, but islets are another story. Trans-species transplant, or xenotransplantation, presents a whole new set of problems and has never been performed successfully in humans. Since pure human islets are hard to come by, the competition among researchers is fierce.

Staying Alive

But even with all the donors in the world, or if we could produce synthetic cells in a test tube, if the islets are not protected from a recipient's immune system they will die. If transplantation were simply a matter of injecting islets haphazardly into the body, diabetes would have been eradicated a decade ago.

Over the years, researchers have tried a number of methods of "tricking" the body into accepting foreign cells. These attempts have involved immunosuppression (giving drugs that disable the patient's immune system) and subjecting cells to extreme conditions in an effort to disarm the markers carried on the cells that identify them to the immune system. Nothing has worked well enough to warrant much excitement for the average person with diabetes. Some recent studies have tried to encapsulate islets in a material that lets "good" elements like oxygen and insulin cross its membrane, while keeping the islet "invisible" to the immune system.

Encapsulation

It is generally accepted that encapsulation will work. Up for debate, though, is what kind of material should be used to encase the cells. In many instances, the body attacks not the islets but the encapsulation itself, covering the material with scar-like fibrous tissue. When this happens, the islet cells suffocate. Therefore, it is vital to find the right kind of material.

Some researchers have used hollow fibers, and one is planning to use sheets of semiporous material which can be placed easily into the body. Although the concept of a semipermeable barrier has been around since the 1950s, it is only recently showing real promise. Attempts have been made with plastic implants, but these are quickly overgrown by the patient's own cells which will then essentially starve the islets. Also, for an islet transplantation method to be considered really revolutionary, it must offer safety for the islets without the use of immunosuppressive drugs. If the encapsulation is really working, the immune system won't know the foreign cells are present in the body.

Of Mice and Men

Some researchers have transferred islets between different species of mice without immunosuppression and have met with favorable results. However, the reason for the success of these projects is shockingly simple-unlike "higher" animals like dogs and humans, rodents do not have a complete immune system. Since rodents only live a couple of years, they have no need for the high-powered immune system that bigger, hardier species require. For this reason, it might be argued that continuing research with rats and mice is pointless. When a rat does not reject a new form of encapsulated islets, the success may not translate to humans or even larger mammals.

When a man gets the heart of a teenage girl who died in a car crash, he must take drugs to prevent his immune system from attacking the girl's heart. However, transplantation between wholly different species-for example, rabbit to monkey-may cause "hyperacute rejection" within moments. Immune cells during "normal" rejection can be compared to a loose group of citizens who band together when a foreign army invades their city. They travel to the site of invasion once they're organized. In hyperacute rejection, the immune cells are like an armed band of guerrillas ready to annihilate the invader the moment it arrives. When this happens, a healthy organ can turn black within five minutes of transplantation. This is why xenotransplantation is not a currently accepted source of islet cells. It is hoped that xenotransplantation between higher animals, like pigs and humans, will eventually offer hope.


Categories: Blood Glucose, Diabetes, Insulin, Islet & Pancreas Transplant, Research



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