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Smart' tissue regenerates brain
By Charlene Laino <mailto:[log in to unmask]> MSNBC
                June 7 - Within two years, Boston researchers plan to embark on a novel
experiment in which they will "re-seed" the damaged brains of patients
suffering from any of a variety of neurological diseases. The seeds: neural
stem cells - the building blocks for all our brain and nervous system cells.
The goal: to sprout healthy brain cells to replace faulty ones, while
coaxing surrounding tissue back to life.                ULTIMATELY, the researchers hope
to grow a virtually unlimited amount of human brain tissue to replace the
diseased neurons of those who have suffered strokes, spinal cord injuries or
other neurological diseases.
In a new study at Harvard Medical School, the scientists have already shown
that, in mice genetically engineered to suffer from human strokes, neural
stem cells have an affinity for the area of brain injury. Once there, the
cells integrate seamlessly into the surrounding brain tissue, maturing into
the type of tissue appropriate for the particular area of the brain.
The research suggests that these cells may be effective in treating a much
broader array of brain diseases than previously anticipated, including
Alzheimer's disease and many childhood brain disorders.
"There is lots of wiggle room in the nervous system, especially at the level
of stem cells," says Evan Snyder, an assistant professor of neurology at
Harvard who is leading the research. "So we can tap into the natural
plasticity of the seeds and exploit them.
"What may already have in our hands is the universal donor brain cell, one
that can direct cells to go where we want them to and to do what we want
them to."
Conditions ranging from inherited defects such as Tay-Sachs disease to
birth-related oxygen deprivation to brain cancer could one day be treated
with neural stem cells, Snyder predicts. And that's not to mention dementia,
Alzheimer's disease, Parkinson's disease and multiple sclerosis - meaning
there are literally hundreds of thousands of patients who could benefit.
Moreover, you could help the unborn. "If prenatal diagnosis showed a brain
disease, I would start as in-utero, with gene therapy, as soon as possible,"
Snyder says.

SEEDING THE LAWN
Snyder compares the diseased brain to a trampled lawn - "perhaps a lawn that
didn't grow right or was destroyed b the kids biking or by the weather."
Just as you would grow new grass by seeding the lawn, you can sprout healthy
tissue by seeding the "broken" brain - with neural stem cells.
Moreover, the stem cells can be genetically engineered to grow super-seeds
that produce a gene that is missing in the brain, for example. In other
words, you can isolate and harvest neural stem cells and use them as just as
they are, or introduce foreign genes through designer engineering, tailoring
the treatment to the problem.
And that is just what happened in mouse and animal studies. In one
experiment, for example, his team removed stem cells from deep within the
forebrain of a fetus several years ago. When they cloned individual cells,
they gave rise to both neurons and their support cells, the glia.
Then, they grafted immature stem cells into different areas of the
developing mouse brain. Following signals from their new environment, the
human stem cells migrated along existing pathways and matured into the type
of neuron and glia appropriate for the particular area.
To produce the super-seeds, the researchers then inserted the gene that
codes for the protein that is missing in patients with Tay-Sachs disease. In
test-tube experiments, the designer stem cells were able to correct the
deficiency underlying the genetic disorder, suggesting that the super-seeds
could indeed supply therapeutic proteins missing in inherited brain
diseases.
In another test, failing brains in mutant mice were shored up by injecting
neural stem cells to replace damaged or diseased cells, he said.
"The findings prove that the brain is more like plastic than we ever
imagined," the Boston researcher said.
Questions still remain. While, in all the experiments, the grafted cells
integrated seamlessly into the surrounding brain tissue, it remains to be
seen if they actually function.
The new study, funded in part by the National Institute of Neurological
Disorders and Stroke, appears in this week's issue of the Proceedings of the
National Academy of Sciences.

GOAL CLOSER TO REALITY
Nevertheless, scientists at the recent meeting of the American Association
for the Advancement of Science in Anaheim, Calif., expressed optimism about
the new work.
The approach brings the goal of harnessing neural stem cells for the
treatment of human disease one step closer to reality, says Mark H.
Tuszynski of the University of California, San Diego, whose is utilizing
other genetic engineering techniques
<http://www.msnbc.com/news/235298.asp>to fight Alzheimer's disease. "We're
beginning to see that we can tailor cells and orchestrate. We can recreate
the brain."








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Bruce A. Hollenbeck
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