Stem Cells Reverse MS-Like Condition In Mice, University of Utah Study
5/16/2014 7:03:22 AM
Mice With MS-Like Condition Walk Again After Human Stem Cell Treatment
May, 15, 2014 – Mice severely disabled by a condition similar to multiple sclerosis (MS) could walk less than two weeks following treatment with human stem cells. The finding, which uncovers new avenues for treating MS, will be published online on May 15, 2014, in the journal Stem Cell Reports.
When scientists transplanted human stem cells into MS mice, they expected no benefit from the treatment. They thought the cells would be rejected, much like rejection of an organ transplant.
Instead, the experiment yielded spectacular results.
“My postdoctoral fellow Dr. Lu Chen came to me and said, ‘The mice are walking.’ I didn’t believe her,” said co-senior author, Tom Lane, Ph.D., a professor of pathology at the University of Utah, who began the study at the University of California, Irvine.
Within a short period of time, 10 to 14 days, the mice could walk and run. Six months later, they showed no signs of slowing down.
“This result opens up a whole new area of research for us to figure out why it worked,” said co-senior author Jeanne Loring, Ph.D., director of the Center for Regenerative Medicine at The Scripps Research Institute in La Jolla, Calif.
More than 2.3 million people worldwide have MS, a disease in which the immune system attacks myelin, an insulation layer surrounding nerve fibers. The resulting damage inhibits transmission of nerve impulses, producing a wide array of symptoms including difficulty walking, impaired vision, fatigue and pain.
Current FDA-approved medications slow early forms of the disease by dampening attacks by the immune system. In recent years, scientists have turned their attention to searching for ways to halt or reverse MS. Such a discovery could help patients with latter, or progressive, stages of the disease, for whom there are no treatments.
Results from the study demonstrate the mice experience at least a partial reversal of symptoms. Immune attacks are blunted, and the damaged myelin is repaired, explaining their dramatic recovery.
“The way we made the neural stem cells turns out to be important,” said Loring, describing the reason behind the novel outcome.
Prior to transplantation, Loring’s graduate student and co-first author on the paper, Ronald Coleman, followed his intuition and grew the cells so they were less crowded on the Petri dish than usual. The change in protocol yielded a human neural stem cell type that turned out to be extremely potent. The experiments have since been successfully repeated with cells produced under the same conditions, but by different laboratories.
Counterintuitively, Lane and Loring’s original prediction that the stem cells would be rejected from the mice, came true. As early as one week post-treatment, there were no signs of the transplanted stem cells in the mouse. What would ordinarily be considered a handicap, turns out to be a significant advantage.
The human neural stem cells send chemical signals that instruct the mouse’s own cells to repair the damage caused by MS. Experiments by Lane’s team suggest that TGF-beta proteins comprise one type of signal, but there are likely others. This realization has important implications for translating the work to clinical trials in the future.
“Rather than having to engraft stem cells into a patient, which can be challenging from a medical standpoint, we might be able to develop a drug that can be used to deliver the therapy much more easily,” said Lane.
With clinical trials as the long-term goal, the next steps are to assess the durability and safety of the stem cell therapy in mice.
“We want to try to move as quickly and carefully as possible,” Lane continued. “I would love to see something that could promote repair and ease the burden that patients with MS have.”
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The research was funded by the National Multiple Sclerosis Society and the California Institute of Regenerative Medicine.
In addition to Lane, Loring, Chen, and Coleman, other authors include Ronika Leang, Alexandra Kopf, Craig Walsh, and Oswald Steward (UC Irvine), Ilse Sears-Kraxberger (TSRI), Oswald Steward, Wendy B. Macklin (University of Colorado, Aurora).
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