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FROM: Eureka Alert

Steve Benowitz or Phyllis Fisher
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Thomas Jefferson University

Jefferson scientists find new way to convert adult human stem cells to
dopamine neurons

Researchers at Jefferson Medical College have found a new way to coax
bone marrow stem cells into becoming dopamine-producing neurons. If the
method proves reliable, the work may ultimately lead to new therapies for
neurological diseases such as Parkinson's disease, which is marked by a
loss of dopamine-making cells in the brain.
Developmental biologist Lorraine Iacovitti, Ph.D., associate director of
the Farber Institute for Neurosciences at Thomas Jefferson University in
Philadelphia and her co-workers had previously shown that by using a
potion of growth factors and other nutrients in the laboratory, they were
able to convert adult human bone marrow stem cells into adult brain
cells. Human adult bone marrow stem cells – also known as pluripotent
stem cells – normally give rise to human bone, muscle, cartilage and fat
cells.

While nearly all cells looked like neurons with axonal processes, they
invariably reverted back to their original undifferentiated state in two
to three days.

Dr. Iacovitti and her co-workers instead attempted to grow the cells in a
different way. Rather than an attached monolayer of skin-like cells, they
grew the bone marrow cells in suspension as neurospheres – groups of
cells early in development – akin to the way neural stem cells are grown.


They found that the newly differentiated cells didn't merely look like
dopamine neurons, but expressed traits of neurons and related cells
called astrocytes and oligodendrocytes – cells derived from neural stem
cells. What's more, the neurons produced tyrosine hydroxylase, an enzyme
needed to make dopamine.

She reports her team's findings October 25, 2004 at the annual meeting of
the Society for Neuroscience in San Diego.

The Jefferson scientists also found a second enzyme involved in dopamine
production, and an important molecule called the dopamine transporter.

Interestingly, Dr. Iacovitti notes, some of the cellular markers that
would be expected to be expressed by new bone marrow cells were present
in bone marrow stem cells grown in the original monolayers, though they
were fewer in number.

"The markers don't disappear," explains Dr. Iacovitti, who is also
professor of neurology at Jefferson Medical College of Thomas Jefferson
University. "The cells seem to have markers of both bone marrow cells and
dopamine neurons all the time. They don't forsake what they normally
would be."

While she can't say for sure whether or not the stem cells grown with the
new method have markers of both bone marrow stem cells and dopamine
neurons, the new dopamine neurons did not revert back to stem cells.

"There are limitations to differentiating adult stem cells the way we
want them – to get them to permanently give up being what they were meant
to be and become neurons," she says. "Maybe this is a way to grow these
stem cells to get them to truly become dopamine neurons instead of just
looking like neurons.

"If we can now appropriately direct the differentiation of bone marrow
stem cells, these cells could provide an abundant source of adult human
neurons for use in the treatment of neurodegenerative diseases," she
says.

http://www.eurekalert.org/pub_releases/2004-10/tju-jsf102504.php

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