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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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