Stem cells and cord injury in rats..effective early but not late..
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spinal cord function.
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TORONTO, March 29 - Stem cells can be used to repair injured spinal cords in rats, as long as the treatment takes place early enough, according to researchers here.
In rats whose spinal cords had been crushed, transplanting neural precursor cells (NPCs) within two weeks of the injury led to better recovery of the ability to walk and use their hind legs, found Michael Fehlings, M.D., Ph.D., of the Krembil Neuroscience Center at the Toronto Western Research Institute here.
In principle, a similar approach could be applied to a large proportion of the approximately 13,000 new spinal cord injuries every year in North America, Dr. Fehlings said in an interview.
On the other hand, he added, the experiments -- reported in the March 28 issue of the Journal of Neuroscience -- showed that the same approach is unlikely to work in the case of chronic spinal injury.
"The timing of this is really important," Dr. Fehlings said. "On the plus side, we've been able to extend the time window to where we were able to use the stem cells about two weeks after injury and they worked."
"What was somewhat sobering was that in the chronic injury, which we defined as about six to eight weeks after injury, the stem cells did not work," he said. One reason the process didn't work in that situation, he said, may be scar tissue formed on the injured spinal cord.
In most human spinal cord injuries, "the break is not complete," Dr. Fehlings said: Some nerve tissue remains intact, but is not effective because it loses its myelin sheath. To duplicate that situation, the researchers crushed, rather than cut, the spinal cords of their animals.
Two weeks later, they transplanted NPCs, together with growth factors and other medications designed to encourage the cells to differentiate into oligodendrocytes, which would then theoretically re-cover the nerve tissue with myelin and improve the function of the spinal cord.
NPCs have been shown to have the ability to differentiate into all of the cells types found in the brain; in this case, roughly half of the transplanted cells became either oligodendrocytes or oligodendrocyte precursors. There was no evidence that any of them became new neurons.
The transplanted mice, the researchers found, developed significantly thicker myelin than either of two control groups -- one group with just a spinal cord injury and one that was given the same treatment with growth factors and other medications, but didn't get the stem cell transplant.
The finding offers "significant hope" for human treatment, Dr. Fehlings said, because it's much easier to cause one type of cell to grow than to rebuild all of the cell types found in the intact spinal cord. "Replacing one cell type is going to be a lot more doable," he said.
But aside from producing the appropriate type of cell, the procedure also gave the injured animals better control of their hind legs, Dr. Fehlings said. On three standard tests, the transplanted rats outperformed the controls.
For example, he said, normal rats easily walk across a meter-long ladder-like grid without missing any of the horizontal supports. Two weeks after transplantation, all three groups of rats missed an average of nine or 10 steps per session. The rats in the control groups didn't improve, but by six weeks after the transplant, the treated rats only missed an average of 6.03 steps. The difference was significant at P<0.05.
The treatment is "not a magic bullet," Dr. Fehlings said. "There is some residual impairment." But even small improvements in mobility could make a "dramatic difference in quality of life" for an injured human, he said.
The work "breaks new ground," commented Oswald Steward, Ph.D., director of the Reeve-Irvine Research Center for Spinal Cord Injury at the University of California at Irvine. In a statement, Dr. Steward said the research shows that "therapeutically useful stem cells can be derived from the adult brain of rodents, and that these cells can be caused to differentiate into the types of cells that are useful for repairing the damaged spinal cord."
When the researchers repeated the experiment, but delayed the cell transplant to eight weeks after the injury -- mimicking a chronic injury -- the transplant did not result in oligodendrocyte growth, re-myelination of nerve tissue, or physical recovery.
That's new and important information, said Moses Chao, Ph.D., of New York University, and shows that "the timing of neural stem cell application therefore is critical to successful therapy in the injured spinal cord."
Primary source: Journal of Neuroscience
Source reference:
Soheila Karimi-Abdolrezaee et al. "Adult Neural Precursor Cells for Repair of Spinal Cord Injury" J. Neurosci 2006; 26(13):3377-3389.
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