On the Cutting Edge: A peek at the medical breakthroughs of tomorrow

Sprouting ‘smart’ brain tissue
By Charlene Laino--MSNBC

Feb. 15 —  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In as-yet unpublished work underway at Harvard Medical School, the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.

“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.

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.

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 to fight Alzheimer’s disease.
“We’re beginning to see that we can tailor cells and orchestrate. We can
recreate the brain.”
--
Judith Richards, London, Ontario, Canada
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