Canadian researchers use stem cells to help spinal-cord injured rats walk
TORONTO (CP) - Canadian researchers have used stem cells to repair spinal cord damage in laboratory rats, restoring significant mobility in the animals and bringing the search for a human therapy another step closer.
A team led by Toronto neuroscientist Dr. Michael Fehlings extracted stem cells from adult mice, which were transplanted into rats whose spines had been crushed. The stem cells developed into one type of cell destroyed by the injury - those that produce myelin, the insulating layer that cocoons the bundle of nerve fibres that make up the cord.
Injuries that crush or compress the spinal cord destroy its ability to regenerate myelin-forming cells, leading to paralysis.
Without the myelin sheath, "nerve fibres don't conduct the signals, they kind of short out and you don't get signals crossing," said Fehlings, medical director of the Krembil Neuroscience Centre at Toronto Western Hospital.
But rats whose spinal cords were injected with adult stem cells and given a cocktail of drugs - growth hormone, cyclosporine to prevent rejection and the anti-inflammatory minocycline - were found to walk with better co-ordination and weight-bearing ability.
As well, researchers were able to get those results even when the stem cells were injected two weeks after the injury; current therapies that attempt to save spinal cord tissue from trauma-induced destruction must be given within hours of injury.
"Our strategy wasn't to get perfect regeneration or to try to regrow the whole spinal cord," said Fehlings. "Our approach was really to try to replace one missing cell type.
"The reason this is significant is that I think this is going to be a very doable strategy if we try to take these types of experiments into patients. Because instead of, say, trying to hit the home run and trying to reconnect all of the severed nerves, here we're taking cells and saying we want them to do one thing . . . to replace the missing myelin-forming cells."
The key to the success appears to be minocycline, a drug used to treat acne in young people, which reduced inflammation of the spinal cord and limited cell damage, said Fehlings, noting that it also appeared to boost survival of stem cells.
"We had a really high survival rate - about a third of the stem cells survived, which is quite high, and about 80 per cent formed myelin-forming cells," he said.
"So we were really encouraged about these results . . . and we think this is going to potentially be a very effective strategy down the road for patients."
Dr. Oswald Steward, director of the Reeve-Irvine Research Centre for spinal cord injury at the University of California, said the concept of using stem cells for spinal cord cell regeneration has been used by other scientists.
But Fehlings' work "breaks new ground in a couple of ways," by showing that adult stem cells work as well as the more ethically controversial fetal or embryonic stem cells and that the drug minocycline improved their survival, Steward said.
"The other thing is he found that you can do it if you inject a couple of weeks after the injury," Steward said from Irvine, Calif. "A two-week period, that puts you in a realm that's clearly feasible in a human application."
"This is an important step along the road. It's incremental, but it's a big step. It increases our understanding of the things we're going to need to do to make these cells work, so I think it's very important."
Fehlings said his team also used a chemical marker to check that the stem cells weren't producing new cells that were growing out of control. Uncontrolled cell growth is the hallmark of cancer, and scientists increasingly believe that malignancies occur when stem cells go awry.
Fehlings predicted that stem cell replacement could be tried in people with spinal cord injuries within five to 10 years.
"Ninety per cent of what we know about spinal cord injury has been learned in the last 15 to 20 years," said Fehlings, whose study appears in Wednesday's edition of the journal Neuroscience.
"And for me, what this indicates is that there really is hope for the future. We don't have the cure for spinal cord injury with this study, but I believe our work has brought us a significant step closer."
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