February 14, 2007

HUMAN STEM CELL TRANSPLANTS MATURE INTO NEURONS AND MAKE CONTACTS IN RAT SPINAL CORD

Human nerve-producing 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 Packard researcher’s laboratory, overturning the long-held notion that spinal cords won’t allow nerve repair.

A report on the experiments will be published online this week at PLoS Medicine, a peer-reviewed online science journal. The work “establishes a new doctrine for regenerative neuroscience,” says Vassilis Koliatsos, M.D., also an associate professor of neuropathology at Johns Hopkins. “It shows that the spinal cord, a part of the nervous system thought incapable of repairing itself, can support the development of transplanted cells,” he added.

“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,” he says. “We're still in the proof of concept stage, but we're making progress and we're encouraged.”

In their experiments, Koliatsos’ team gave anesthetized rats a range of spinal cord injuries able to injure or kill motor neurons. As a control, they performed sham
surgeries. The varied experimental conditions showed 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 the varied surgeries, 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 in the damaged cords than they had injected, meaning the transplanted cells not only survived but divided at least twice to form more cells.

Moreover, says Koliatsos, 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 developed into support cells—glial cells—rather than nerve cells, though the majority became mature nerve cells. Upon examination under high-powered microscopes, the nerve cells appeared to have made contacts with the rat's own spinal cord cells.

The research was funded by the Robert Packard Center for ALS Research at Johns Hopkins, the National Institute of Neurological Disorders and Stroke and the Muscular Dystrophy Association. 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 of Rockville, Md.

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