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

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Duke Health News 919-660-1306

DALLAS, TX -- 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.

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