Nerve cells grown from human embryonic
stem cells and injected into the brains of rats
with a syndrome mimicking Parkinson's disease significantly
reduced the animals' symptoms, but the treatment
also caused tumors in the rodents' brains, scientists
reported yesterday.
Researchers said the work showed both the potential
benefits and risks of human embryonic stem cells,
which have been highly touted for their capacity
to replace diseased tissue but are controversial
because they are derived through the destruction
of human embryos.
"The behavioral data validate
the utility of the approach. But it also raises
a cautionary flag and says we are not ready for
prime time yet," said lead researcher Steven A.
Goldman, a professor of neurology and neurosurgery
at the University of Rochester Medical Center.
Goldman said he suspected that with
modest changes in technique, researchers will be
able to keep the benefits of the treatment while
eliminating or reducing the chances of getting
the cancerlike growths. But he conceded that much
more basic research would have to be done before
scientists -- or regulators -- were likely to be
convinced of the approach's safety.
In the experiments, Goldman and colleagues
from the Weill Medical College of Cornell University
in New York treated laboratory-cultured human embryonic
stem cells in a new way that coaxed many to become
a kind of neuron that produces dopamine, a neurotransmitter.
Those cells are gradually lost in Parkinson's disease,
depriving the body of that essential chemical messenger.
The disease causes motor problems
such as trembling and muscle rigidity and a gradual
decline in mental functioning.
The team injected the cells into
the brains of rats, which had been given a chemical
that causes damage similar to that seen in Parkinson's.
The new cells integrated into the animals' brains
and produced copious amounts of dopamine. As a
result, the animals' motor coordination improved
almost to the point of being normal, according
to the report in yesterday's online edition of
the journal Nature Medicine.
But when the animals were autopsied
after three months and their brains were examined
microscopically, the team found multiple tumors,
indicating that some of the injected cells did
not settle into the job of being neurons but rather
had begun to grow uncontrollably.
The results were similar to those
of other experiments published Oct. 12 in the online
journal Stem Cells by a team led by Ole Isacson,
a Harvard Medical School professor of neuroscience
and neurology. In that case, the stem cells were
cultivated differently, produced less dopamine
and had fewer beneficial effects. But some grew
out of control.
"I think it is a terrific demonstration
that we are midway between earliest discovery and
clinical application," Isacson said Friday.
Goldman and Isacson said they are
developing technologies for culling from a developing
stem cell population those cells that are not fully
committing themselves to becoming neurons -- or
selecting such fully committed cells from a larger,
mixed population.
"We still have so little experience
with these cells, but if we keep doing the work
and we do it carefully, then I believe that in
the long run it will help patients," Isacson said.
Thomas Okarma, president of Geron,
a California company that hopes to gain Food and
Drug Administration permission to treat spinal-cord-injury
patients with modified embryonic stem cells next
year, said his company's cells have shown no sign
of causing tumor growth in any of its animal studies.
But he said the FDA has asked for
additional extensive data on exactly that question
before it will give its final okay.
"What they worry about, and rightly
so, is there are rogue undifferentiated cells lurking
in the cell population that we haven't detected," Okarma
said.
Geron cultivates its embryonic
stem cells differently than others, he said,
adding that no tumors have been seen in animals
up to nine months after injections into the rodents'
injured spinal cords. Moreover, he said, the
cells survive and help the animals recover, in
part by secreting special factors that spur new
nerve growth around the injury.
Link to complete article http://www.washingtonpost.com/wp-dyn/content/article/2006/10/22/AR2006102200928.html
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