OT Mouse pancreas may lead to diabetes treatment

Mouse pancreas may lead to diabetes treatment


By CAROLYN ABRAHAM
From Monday's Globe and Mail


POSTED AT 9:49 PM EDT Sunday, Aug 22, 2004










Graduate students at the University of Toronto have boosted hopes for
an effective diabetes treatment after growing insulin-producing tissue from
the single cell of a mouse pancreas.

At first blush, the result may appear to be mainly big news for
diabetic mice. But there has been considerable debate in the science world
as to whether the pancreas of any mammal, mouse or human, has the biological
goods to generate new insulin-producing cells.

So far, no experiment has proved that the pancreas contains stem
cells, those promising and controversial cells capable of growing into any
tissue type in the body, making the Toronto study an exciting lead in
finding an abundant insulin-cell source for transplant into diabetes
patients.

"From a single cell, we have been able to grow thousands of cells,"
said Simon Smukler, a doctoral student and one of the lead authors of the
report published Monday in Nature Biotechnology.

The Toronto researchers have also grown nerve cells, including
neurons, from their single mouse cell. But it is not yet clear if they have
discovered actual stem cells or special precursor cells that give rise to
the various cells of the pancreas.

Pinpointing a limitless supply of pancreatic cells that make insulin
has become urgent business with the success of the so-called Edmonton
Protocol, pioneered at the University of Alberta.

Doctors there have been transplanting insulin-making cells, also known
as islets, into Type 1 diabetes patients and literally eliminating their
need for daily insulin injections. Some patients have now been freed of
their insulin dependence for well over a year.

What is more, researchers announced this summer that Canada's results
have been replicated in the United States and Europe in the first
international trials of Edmonton's breakthrough treatment.

But the protocol relies on harvesting islet cells from the pancreas of
human cadavers and the supply of donors falls far short of the demand to
treat diabetes.

"The Edmonton Protocol looks like a pretty good cure. But if these
islet transplants are the way to go, the question is, where are these cells
going to come from?" asked Ronald Worton, head of Canada's Stem Cell
Network, which funded the Toronto project along with the Canadian Institutes
of Health Research.

For this reason, the Toronto study adds to the growing sense that stem
cells will provide the answer, Dr. Worton said.

"I think it's true that diabetes is going to turn out to be a main
focus of Canada's stem-cell efforts," he said.

Type 1 diabetes patients, who are usually diagnosed as children,
cannot produce their own insulin, which carries sugar to the body's cells
where it is essentially turned into fuel.

Mr. Smukler is hesitant to describe the cells plucked from the mouse
pancreas as actual stem cells because it is unclear whether these cells do
indeed possess the defining hallmarks of stem cells, meaning they can
multiply indefinitely and truly become any tissue type, from lung to
ligament.

So far, Mr. Smukler and his colleague Raewyn Seaberg, working in the
lab of scientist Derek van der Kooy, have grown from their single pancreatic
mouse cell eight other types of pancreatic cells, including neurons.

Neurons, the workhorses of the nervous system, are found in the
billions in the brain, but are also thought to reside in the pancreas. So
the researchers cannot yet be certain of the versatility of their
"precursor" cells.

As well, the researchers suggest in their paper that they may not yet
have found the perfect lab-dish conditions to determine if their precursor
cells do have the power to produce an infinite supply of cells.

Still, Mr. Smukler noted that no other experiment has found precursor
cells in the pancreas that can multiply and morph into those that make
insulin.

"No one has done this in the human pancreas, or the mouse," he said.

The next step is for the Toronto researchers to investigate how well
their insulin-producing cells perform in the bodies of diabetic mice.

Speaking of the Toronto work, Dr. Worton said, "The research offers
considerable new hope for people living with diabetes."