In the fall of 2010, a team of scientists in California injected human stem cells into the spinal cords of mice with a condition similar to multiple sclerosis, expecting the mice to reject the cells like they might an organ transplant.
That was the point of the research — to better understand the common problem of stem cell rejection, explained Tom Lane, a University of California, Irvine pathologist now working at the University of Utah.
About two weeks after the injections, however, Lane received an unexpected call from his postdoctoral fellow, Lu Chen.
"She said, ‘These mice are walking,’ and I thought, ‘I don’t believe you,’" recalled Lane, who went down to the lab to see for himself. "Sure enough, there were groups of mice that had gone from being paralyzed to walking around the cage."
Repeated experiments had the same results, which were published Thursday in the journal Stem Cell Reports. The study was funded by the National Multiple Sclerosis Society and the California Institute for Regenerative Medicine.
What works in mice doesn’t always work in humans. But the findings point to a possible new avenue for treating multiple sclerosis (MS), a debilitating disease affecting more than 2.3 million people worldwide.
"This result opens up a whole new area of research for us to figure out why it worked," said co-senior author Jeanne Loring, director of the Center for Regenerative Medicine at The Scripps Research Institute in La Jolla, Calif. "We spent the last year convincing ourselves that the amazing results we saw were reproducible. It was just such a surprise. We’re really into mystery time now."
MS is a disease in which the immune system attacks and erodes myelin, a fatty protective sheath surrounding nerve fibers. Damage to this insulating layer disrupts the transmission of nerve impulses, resulting in an array of debilitating symptoms, from numbness and tingling to blindness and paralysis.
Today’s treatments, such as anti-inflammatories and muscle relaxants, mostly manage symptoms.
There are drugs to suppress patients’ immune systems and prevent white blood cells from infiltrating the brain and spinal cord and ravaging the myelin sheath, which can slow progression of the disease. But no therapies exist to repair damaged nerve tissue, though emerging therapies are being tested in humans.
Lane’s mouse study contributes to this growing field, said John Foley, director of the Rocky Mountain MS Clinic and chief of neurology at Intermountain Healthcare’s LDS Hospital. "It needs to be applied to humans, but for the technique to have had this much of an impact is significant. We’re encouraged by this."
Stem cells have long carried the promise of replenishing or repairing damaged tissue. They’re used, for example, to regenerate the immune systems of cancer patients who have received near-lethal doses of chemotherapy.
But stem cells are often rejected as foreign by the immune system, a barrier to their use in treating all kinds of diseases.
Lane and Loring set out to understand this process, and injected 96 mice with human embryonic stem cells. The mice had virally-induced MS and fully functioning immune systems.
As expected, "the human cells were rejected. We don’t see them after 10 days of injection," Lane said.
But within that short time frame the cells send chemical signals instructing the mouse’s own cells to repair the damage caused by MS.
Within ten to 14 days, symptoms were partially reversed in 73 percent of the mice. Immune attacks were blunted and damaged myelin was repaired, resulting in regained motor skills. Six months later, they still showed no signs of slowing down.
"We saw a dramatic stop in the spread of demyelination and extensive re-myelination, or repair of the myelin sheath," said Lane, describing the findings as "a happy accident."
Also a fluke: the type of neural precursor cells used, which were grown by a graduate student who had tweaked the recipe from one that had been published.
"We had so many lucky breaks, the right people and the right cells by accident," Loring said.
Whether the benefits last is uncertain and will be the subject of future studies.Next Page >
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