Linda, Thanks for the videos of the rat and thanks to that rat.  Ray
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Sent: Wednesday, June 21, 2006 6:02 PM
Subject: Article and video: Neurons from stem cells go the distance


Neurons From Stem Cells Go the Distance
By Constance Holden
ScienceNOW Daily News
21 June 2006

See videos of the rats before and after treatment at:
http://www.hopkinsmedicine.org/Press_releases/2006/Mousevideo.html

"For the first time, stem cell researchers have succeeded in getting
transplanted nerve cells to establish connections with other neurons
to improve movement in paralyzed rats. The success is thanks to
neurons cultivated from embryonic stem cells and the right "cocktail"
of ingredients to guide cell development. Earlier experiments have
improved movement in paralyzed rodents, but the gains have been from
indirect contributions by the cells and not from the generation of
new neurons.
The team, led by neurologist Douglas Kerr, cultivated rat embyronic
stem cells in a dish until they developed into neural precursors. The
researchers then injected 60,000 of the cells into the spinal columns
of rats that had been paralyzed by the injection of a virus. The rats
were then divided into eight treatment groups of 15 animals each to
test slightly differing combinations of chemicals that would allow
the precursor cells to take on their desired roles.

Co-author Jeffrey Rothstein explains that for a precursor cell to
become functional, it first has to differentiate into a motor neuron.
Then it has to develop an axon that can penetrate "this huge wall of
white matter," the outside covering of the spinal column. Finally,
that axon has to grow a long way to make connections with neurons in
leg muscle.

Comparing slightly different cocktail combinations, the researchers
found that three chemicals were needed to coax the neurons to make
the necessary transitions. Daily injections of two of them, dibutryl
cyclic AMP and Rolipram, were given to help neurons overcome factors
that inhibit their ability to break through the spinal cord. The
third, a powerful growth factor called GDNF, was later injected into
sciatic nerves to lure the axons to reach out to peripheral muscles.

The cells that make the grade are still rare: Only about 20% of those
injected into the animals developed into motor neurons. Of those,
less than 1% made it out of the spinal column. Only a few hundred of
the original 60,000 eventually made it all the way to form new
neuromuscular junctions, says Rothstein. But that was enough to bring
about partial but significant recovery of function in 11 of 15 rats
in the group with the winning cocktail, the scientists report in a
paper published online in Neurology on 26 June. The scientists now
plan to try the experiment using pigs, injecting them with neural
precursors developed from human embyronic stem cells.

***This is a "very exciting paper," says University of Wisconsin stem
cell researcher Clive Svendsen. "It's really stimulated everybody in
the field." He says the success of the experiment underscores the
importance of having human embryonic stem cells available for
research. "Of all the stem cells it's really only the embryonic stem
cells that can make motor neurons."
http://sciencenow.sciencemag.org/cgi/content/full/2006/621/1

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