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[IP] Pig cells offer hope on DM

Article from the June 29, 2001 Dialogue from Duke University

Transplanted cells keep diabetic baboon off insulin

Duke researchers reported June 15 that specially
encapsulated insulin-producing pancreas cells from
pigs have kept a diabetic baboon from needing insulin
for more than nine months.  If this approach continues
to show success in similar experimental models, the
researchers believe that trials involving humans with
insulin-dependent diabetes could begin within a year.

The researchers coated islet cells taken from pig
pancreases with a complex carbohydrate know as
alginate and injected the resulting spheres into the
abdominal cavity of a diabetic baboon.  The cells
reacted properly to changing levels of glucose in the
blood and secreted appropriate amounts of insulin to
ensure normal glucose metabolism.

Insulin, a hormone produced and secreted by
specialized pancreas cells called islets of
Langerhans, converts sugars, starches and other foods
into the energy needed for everyday life.  The islets
do not function properly in people with
insulin-dependent, or Type 1, diabetes.  The patients
must have injected insulin to stave off the long-term
effects of improper glucose metabolism, which includes
blindness, kidney disease, heart disease, nerve
damage, limb loss and potentially death.

"After we confirmed that the baboon was indeed
diabetic, we surgically placed the encapsulated islets
into the animal's peritoneal cavity," said Dr. William
Kendall Jr., senior surgical resident at Duke, wo
prepared the results of the team's research for
presentation June 15 at the bi-annual scientific
meeting of the International Pancreas and Islet
Transplant Association.  "To date, the animal's blood
sugar levels have remained in the normal range, and it
hasn't required any additional islet cell therapy,"
Kendall said.  "We are very encouraged by these

Five more baboons are in various stages of study at

According to Dr. Emmanuel Opara, associate research
professor of experimental surgery and cell biology,
who began and leads Duke's islet cell transplant
program, this approach promises a practically
unlimited supply of islet cells that could put an end
to the daily routine of multiple injections for the
more than 1 million Americans with Type 1 diabetes.
Islet cell transplantation could also help
approximately one-quarter of the 15 million Americans
with Type II (adult onset) diabetes who require daily
insulin injections.

A majority of people with Type II diabetes are not
candidates for islet cell transplants, since the root
of their disorder is not improper production of

"We envision being able to place these islets within
the abdomen of humans using existing laparoscopic, or
minimally invasive techniques," Opara said.  "At this
point we do not know how often patients with diabetes
would need this therapy, but the baboon data to date
are very encouraging.  The first baboon is still
diabetes-free after only the initial injection."

During the late 1990's , Opara's team developed the
technique to envelope the islets within an alginate
sphere.  After isolating the insulin-producing islet
cells from the rest of the pig pancreas tissue, they
are bathed in the alginate solution and gently forced
through a system that creates  a protective sphere
around each islet.

"The spheres have surface 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," Opara
said.  "The spheres could be placed anywhere in the
body where they come into contact with blood or other
bodily fluids."

In the case of the first baboon, it required about
250,000 islets taken from three pigs.  While it is not
yet know how many pig pancreases would be needed to
yield enough islets for a himan, there are more than
90 million pigs used for food production each year in
the United States, more than enough to treat the
number of Americans with diabetes, the researchers

Once the baboon became diabetic, its fasting glucose
levels jumped from from about 100 milligrams per
decaliter of blood to about 400 mg/dL.  During the
nine-month period following the islet cell transplant,
glucose levels averaged 115 mg/dL.   The researchers
did not detect any signs that the baboon's immune
system reacted to the pig islets.

The pancreas is a complex gland-it not only regulates
blood glucose levels, but also secreted enzymes that
are crucial to digestion.  This complexity has led to
difficulties in developing a riliable animal model to
study ways to treat the disease.

Other Duke members of Opara's team include Drs. Brad
Collins, Hasan Hobbs and Randy Bollinger.  The islet
cell research is supported by the Department of
Surgery and MicroIslet, Inc., a San Diego-based firm
that has licensed the rights of this technology from
Duke.  None of the Duke team members has a financial
interest in MicroIslet.
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