Old affliction meets new science
Scientists from across Canada try to uncover how brains can repair
themselves after strokes with stem cells from their own bodies

Tom Spears

The Ottawa Citizen
Tuesday, March 25, 2003

The brain withers during a stroke, as its blood supply is cut off and
oxygen-starved neurons die. Once dead, these delicate cells are gone
forever. People lose the ability to walk or talk or even to
understand.

Now, a $1.5-million project will link medical researchers across
Canada in an unprecedented attempt to learn how the brains of stroke
patients may repair themselves with stem cells from their own bodies.

Twenty-five scientists in Ottawa and seven other cities hope to train
stem cells from diverse parts of the body to travel to the brain's
injured area, form themselves into brain cells, connect with other
neurons -- and actually think.

If it works, the achievement would be enormous. Fifty thousand
Canadians will suffer a stroke this year, and 300,000 are living with
the after-effects of an attack on the brain.

This is where an age-old affliction meets a new wave in science.

Stem cells are the body's construction materials. They are unfinished
cells held in reserve, to be turned into bone or muscle or other
specialized cells later, as the body grows or needs repairs.

But they are also some of the least understood and elusive cells in
our body.

The Canadian Stroke Network and the Stem Cell Network are both based
at the University of Ottawa, but link many labs and scientists across
the country. This week they're announcing the start of Adult Stem
Cells to Treat Stroke, a plan with an ungainly name that undertakes
the most delicate work.

Stem cells are a strong area for Canadians: Neural stem cells, for
instance, were discovered here in the first place, as were stem cells
in the retina of the eye.

Now scientists in Ottawa, Toronto, Calgary, Edmonton, Lethbridge,
London, Halifax and St. John's, Nfld. will try to put those cells to
use fixing brain damage in animals. They will use a breathtakingly
diverse set of materials -- stem cells that form in the brain along
with others formed in the skin and in the bone marrow.

Oddly, these cells from different areas aren't as different as they
might seem. Fully formed neurons are nothing like skin or bone
marrow. But cells that begin their existence in these different
places don't necessarily stay there long enough to grow up. Like
people, they can move to a new neighbourhood and turn out quite
differently, so that a stem cell from skin becomes a brain or muscle
cell.

Doctors call this "plasticity." It's new and still controversial.

"But if it's true and it holds up, this could be of phenomenal
importance. You might be able to take stem cells from a part of the
body where there's no disease and use them to treat and regenerate
tissue in another part of the body where there is disease," says Ron
Worton, scientific director of the Stem Cell Network.

"What is exciting us is that they all seem to have, to a large or
small degree, the ability to become brain cells," said Antoine Hakim,
scientific director of the Canadian Stroke Network. "The research
project at one level is to understand the biology ... How can we
encourage them to become brain cells?

"And then the question is, can we increase their availability to the
brain?"

This seems to mean putting the would-be brain cells into the
bloodstream and finding ways to aim them, so that when they reach the
brain they'll stop there, physically enter the brain's injured area
and start developing into working neurons that communicate with
established brain cells. It seems likely the brain does some of this
work itself, calling stem cells to come and enter its injured area.

The final question is the simplest: Will any of this help the
patients to get out of wheelchairs? Talk again? Feed themselves?

At the University of Calgary, the progress has already begun with
rats that have grown back working brain cells -- and regained the
ability to move their legs -- after suffering damage similar to a
stroke.

Calgary researchers caution the advance is still in its early stages.
Yet they are clearly elated.

The brain has a supply of stem cells naturally, and when there's
damage it somehow senses the need to send these cells to the injury
site for repairs.

Yet in the case of a stroke, the number it sends "is vanishingly
small," Calgary neuroscientist Sam Weiss explains.

But in rats, his team is adding growth factors -- natural chemicals
produced in the body to stimulate the building of new tissue. An
extra dose of a growth factor can boost the number of stem cells sent
to the stroke area by close to 10 times.

"We've got to the point where we know you can get some sort of
functional recovery" caused by new brain tissue forming, says Dr.
Weiss. So far this only works in rats treated within a few days of
the brain injury.

Now they are measuring whether the animals can move their limbs in a
useful way.

"Can they even reach to grasp their food, for example? And that's
very relevant to what happens when a human has a stroke."

In the end, they'll test this kind of brain repair against repairs
done with stem cells from the bone marrow and skin, "using the same
animals, treated the same way and studied the same way," he says.
"It's the first of its kind, doing that kind of a comprehensive, head-
to-head comparison."

The whole project depends on the kind of cross-country co- operation
you can't find in much of the world.

Last month, a Canadian public health expert just back from years in
the United States was addressing a conference in Montreal. "If you
could put all the genome experts in the United States in one room
..." he began, then stopped. Of course, he added, "they'd probably
kill each other."

His point was that Canada doesn't work that way. Scientists here get
along. Maybe we're a more civil society; maybe, says Dr. Hakim. Our
winters are so tough that we have to stick together.

"We actually like working together."

No one in the project knows where it will lead, yet they say any
progress would be welcome.

"The definition of a stroke is sudden. You're not prepared for it,"
says Dr. Hakim. "In a very short period of time you go from a fully
productive member of the family to being handicapped."

Weakened arms and legs are more or less accepted; much more
frustrating for the patient and the whole family is the new
difficulty in thinking and making decisions.

Half the family members who take care of stroke patients seek
psychiatric help for depression within a year.

Dr. Hakim has seen surveys where patients rate their health on a
scale of where five means perfect life and zero means death. Stroke
victims sometimes pick a negative number.

"They're rather be dead," he said. "So when you ask: What can we
(stem cell researchers) give back with this? The answer is, anything
would be OK. The ideal is like when you break a bone: Years later
it's only a memory of something horrible."

SOURCE: The Ottawa Citizen
http://www.canada.com/ottawa/story.asp?id=%7BE77030DD-39A8-447F-8DD2-
C2C1BC5C3079%7D

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