Human nerve stem cells transplanted into rats' damaged
spinal cords have survived, grown and in some cases
connected with the rats' own spinal cord cells in a Johns
Hopkins laboratory, overturning the long-held notion that
spinal cords won't allow nerve repair.
A report on the experiments, published online last
week at PLoS Medicine, "establishes a new doctrine for
regenerative neuroscience," said Vassilis Koliatsos,
associate professor of neuropathology at Johns Hopkins.
"The spinal cord, a part of the nervous system that is
thought of as incapable of repairing itself, can support
the development of transplanted cells.
"We're still in the proof-of-concept stage," he said,
"but we're making progress, and we're encouraged. We don't
yet know whether the connections we've seen can transmit
nerve signals to the degree that a rat could be made to
walk again."
In their experiments, the scientists gave anesthetized
rats a range of spinal cord injuries to lesion or kill
motor neurons, or performed sham surgeries. They varied
experimental conditions to see if the presence or absence
of spinal cord lesions had an effect on the survival and
maturation of human stem cell grafts. Two weeks after
lesion or sham surgery, they injected human neural stem
cells into the left side of each rat's spinal cord.
After six months, the team found more than three times
the number of human cells than they had injected in the
damaged cords, meaning that the transplanted cells not only
survived but divided at least twice to form more cells.
Moreover, Koliatsos said, the cells not only grew in the
area around the original injection but also migrated over a
much larger spinal cord territory.
Three months after injection, the researchers found
evidence that some of the transplanted cells had developed
into support cells rather than nerve cells, while the
majority became mature nerve cells. High-powered
microscopic examination showed that these nerve cells
appear to have made contacts with the rat's own spinal cord
cells.
The research was funded by the National Institute of
Neurological Disorders and Stroke, the Muscular Dystrophy
Association and the Robert Packard Center for ALS Research
at Johns Hopkins.
Authors on the paper are Jun Yan, Leyan Xu, Annie M.
Welsh, Glen Hatfield and Koliatsos, all of Johns Hopkins;
and Thomas Hazel and Karl Johe of Neuralstem, Rockville,
Md.
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