Mice with MS-Like Condition Walk Again After Human Stem Cell Treatment

At the start of a recent experiment, a group of mice were so disabled by a disease similar to multiple sclerosis (MS) that they had to be hand-fed. But just two weeks after treatment with human neural stem cells, they were walking on their own.

Funded by the National MS Society, the study’s results, published online today in the journal Stem Cell Reports, surprised researchers who expected the stem cells to be rejected. Instead, the mice completely regained motor function, and six months later they still showed no signs of slowing down.

“My postdoctoral fellow Dr. Lu Chen came to me and said, ‘The mice are walking.’ I didn’t believe her,” said co-senior author, Thomas Lane, a professor of pathology at the University of Utah, in a press release. He began the study with Chen at the University of California, Irvine.

The team injected human neural stem cells into the spines of mice, Lane told Healthline. Since mice do not get MS, researchers had to infect them with a similar disease. Many MS studies rely on a disease model known as experimental autoimmune encephalomyelitis (EAE), but not in this case, said Lane.

For this study, they used Mouse Hepatitis Virus (MHV) which causes an inflammatory condition that attacks the myelin covering of nerve cells, much like MS does in humans. “We used the viral model, as viruses have long been proposed to trigger MS in genetically susceptible individuals,” Lane said. The viral version of the MS-like disease also causes greater disability than EAE.         

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A Recipe for Success

“The way we made the neural stem cells turns out to be important,” said Jeanne Loring, co-senior author and director of the Center for Regenerative Medicine at The Scripps Research Institute in La Jolla, Calif., in a press release.

Loring’s graduate student and co-first author of the paper, Ronald Coleman, experimented with different ways to grow the stem cells in the lab.

The researchers believe that Coleman’s idea to produce the cells in a less crowded petri dish resulted in more robust and potent cells. Lane said, “In my opinion… they are immunomodulatory in that we see a dramatic and sustained reduction in neuroinflammation and they also secrete factors that may enhance remyelination.”

Curiously, as predicted by Lane and Loring, the human stem cells were actually rejected. As early as one week after transplantation, no sign of the human cells remained in the mouse bodies. Rather, the cells had successfully flipped a switch, signaling the mouse’s own cells to begin the process of repairing the myelin damage. What might have been a devastating failure turned out to be a huge advantage.

This isn’t a chance outcome, however. Using the same method contrived by Coleman to grow the human stem cells, the experiment has been repeated successfully in other laboratories.

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A Perplexing Rejection

Why these human cells triggered myelin repair within the mice's bodies, but were rejected once their job was done, still puzzles the researchers. 

Trying the same experiment using neural stem cells from mice that were mismatched donors, “the cells are rejected and we do not see a similar recovery. We are currently examining mouse [embryonic stem cells] and iPSC-derived [neural progenitor cells],” said Lane, “to assess if it is the origin of the cells that may be critical to clinical and histologic outcome.”

Before they can begin studies in human volunteers, the researchers will first need to experiment using other models of MS in mice. “Of course, we would love for this to have a similar effect in MS patients (either RRMS or progressive forms of the disease),” Lane said, “but we want to gather as much information using preclinical models first.” If early studies in mice continue to be successful, Lane is hopeful that human trials might begin within a few years.

For MS patients, the fact that the mice are once again walking is promising news. Although there are 10 approved disease modifying therapies for MS, none of them have proven effective for treating progressive MS. With research studies like this one shifting the focus to the repair of damaged myelin, effective treatments for those who are more severely disabled by MS may be on the horizon.

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