|Send to printer »|
GEN News Highlights : May 16, 2014
Human Stem Cells Get Mice with MS-Like Disease Walking
A multi-university research team reports that mice severely disabled by a condition similar to multiple sclerosis (MS) were able to walk less than two weeks following treatment with human neural stem cells. Their study (“Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis”), which the scientists say uncovers potential new avenues for treating MS, is published in Stem Cell Reports.
When the researchers transplanted human neural stem cells into the MS mice, they expected no benefit from the treatment. They thought the mice would reject the cells, much like rejection of an organ transplant. What was to be a routine experiment instead yielded spectacular results on the first try, according to Tom Lane, Ph.D., professor of pathology at the University of Utah. He began the study with co-first author Lu Chen, Ph.D., at the University of California, Irvine.
“My postdoctoral fellow Dr. Chen came to me and said, ‘The mice are walking.’ I didn’t believe her,” said Dr. Lane. Within 10 to 14 days, the mice had regained motor skills. 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,” added Jeanne Loring, Ph.D., co-senior author and director of the Center for Regenerative Medicine at The Scripps Research Institute in La Jolla, CA. “We’ve long forgotten our original plan.”
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.
“We show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 post-transplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination,” wrote the investigators.
They continued: “Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4+CD25+FOXP3+ regulatory T cells (Tregs) within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T-cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments.”
“The way we made the neural stem cells turns out to be important,” explained Dr. Loring, describing the reason behind the novel outcome. Prior to transplantation, Dr. Loring’s graduate student and co-first author on the publication, 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, Drs. 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 mice. In this case, 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 Dr. 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 Dr. 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,” continued Dr. Lane. “I would love to see something that could promote repair and ease the burden that patients with MS have.”
To enjoy more articles like this from GEN, click here to subscribe now!
© 2016 Genetic Engineering & Biotechnology News, All Rights Reserved