Complex Carbohydrate Spheres Protect Islet Cells; Allow Them To Function Properly

November 08, 1997

DALLAS -- Duke University Medical Center researchers have developed special spheres to protect insulin-producing pancreatic islet cells, an achievement they feel improves the possibility of islet cell transplantation as a viable treatment for diabetes.

The development of these spheres, which are formed from a complex carbohydrate known as alginate, appears to solve one of the major problems hindering successful islet cell transplants.

"These spheres have pores that are large enough to allow glucose to enter and insulin to exit, but are small enough to keep immune system cells from entering the spheres and attacking the islet cells," said Emmanuel Opara, assistant research professor of experimental surgery, who heads Duke's islet cell research.

The researchers also found that when tested in experimental animal models, the isolated islet cells produced insulin appropriately in response to changes in glucose levels.

The results of the Duke research were prepared for presentation Saturday (Nov. 8) at the 31st annual meeting of the Association for Academic Surgery in Dallas by Opara and Dr. Marc Garfinkel, former surgical fellow at Duke and now at the University of California at San Diego.

Insulin, a hormone produced and secreted by specialized cells in the pancreas called islets of Langerhans, converts sugars, starches and other foods into the energy needed for everyday life. These islets do not function properly in insulin-dependent, or Type I, diabetes. These patients must inject insulin to stave off the long-term effects of the disease, which include blindness, kidney disease, nerve damage, limb loss and potentially death.

The experimental islet cells are isolated from a donor animal pancreas by treating the gland with enzymes that digest all tissue except islet cells. The isolated cells are then added to an alginate solution.

Using a Duke-developed droplet generator, the alginate solution is forced through a fine needle, creating tiny spheres that harden as they drop into a calcium solution. Each sphere usually contains one or two cells, Opara said. At this point in the process, the entire sphere is a solid. The spheres are then coated with an outer layer of alginate, separated by an amino acid layer.

"We then chemically treat the spheres, in a process called chelation, causing the initial layer of alginate to liquefy," Opara said. "The liquid center provides an ideal environment for the islets to function within a protective shell."

The researchers tested the ability of these islets to secrete the appropriate amounts of insulin when challenged with different levels of glucose in three settings: one group with liquefied sphere cores, the second group with unliquefied cores, and third group with islets that had been cultured for 24 hours in a solution of nutrients and antibiotics, but without a liquefied core.

"The islets in the first group responded as normal islet cells would in response to changing glucose levels, while the second group showed no response at all," Opara said. "The third group showed a small, but significant response, which leads us to believe that culturing may enhance their function."

Surgeons have transplanted more than 7,000 human pancreases since 1966, which has permitted many diabetics to stop injecting insulin, but there are not nearly enough organs to go around. It is estimated that more than 1 million Americans with Type I diabetes could benefit immediately from such a transplant; however, only about 5,000 pancreases become available each year for transplantation.

Scientists developed the method for isolating islet cells in the late 1960s. Since then, about 200 procedures have been performed; however, in many of the patients, the islets stopped working and the patients returned to injectable insulin.

The chemical process employed to isolate the islets can take as many as three to four human pancreases to provide the approximately 1 million islet cells needed to survive transplant. For this reason, researchers have looked to other sources for islet cells.

Pigs are an attractive source of islets, said Duke's Dr. Robert Harland, transplant surgeon and member of the research team, since more than 90 million are killed each year for food. Researchers at Duke are working with specially bred pigs with human genes inserted into their genetic make-up, believing that when the tissue is transplanted into humans, it will escape detection by the immune system.

Harland said that while further tests are needed to better understand potential immune response issues and the optimum site in the body to implant the cells, islet cell transplants could become a clinical reality in the near future.

"Surgically, we would probably place the cells laparoscopically somewhere in the abdomen, which is much less invasive than a pancreas transplant," Harland explained. "At this point, we don't know how long the islets would continue to function. But if we needed to implant new cells every six months to a year, that would still be better for the patient than injecting insulin multiple times during the day.

"Research has shown how important close control of glucose levels is for diabetics in preventing the negative outcomes of the disease," Harland said. "Islet cell transplants have the potential to provide this level of glucose control."

Harland predicted that the likely first patients to receive such transplants will be Type I diabetics with a functioning kidney transplant since they will already be on anti-rejection medication.

A majority of Type II diabetics are not candidates for islet cell transplants, since the root of their disorder is not improper production of insulin, but rather the ability of receptors in the body to properly process insulin.

Duke's islet cell research is currently being supported by its department of surgery.

Duke University Medical Center

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