MS mice regain ability to walk after stem cell therapy
Multiple sclerosis is an often disabling disease of the central nervous system that interrupts information between the brain and the body. Now, in mice crippled by a similar autoimmune disease, scientists have shown that they were able to walk and run after their spinal cords were implanted with human stem cells.
The researchers - from The Scripps Research Institute (TSRI), University of Utah and University of California-Irvine - say their findings could potentially lead to new ways of treating the condition in humans. They publish their results in the journal Stem Cell Reports.
According to the authors, multiple sclerosis (MS) affects more than two million people worldwide. It is a result of certain immune cells - called T cells - invading the upper spinal cord and brain, and causing inflammation and the loss of myelin, which is an insulating coating on nerve fibers.
When the affected nerve fibers lose the ability to properly send electrical signals, symptoms such as limb weakness, numbness, fatigue, vision problems, memory difficulties and slurred speech can occur.
Dr. Jeanne Loring, study co-leader from TSRI, explains that, even after the bodies of the mice from their experiment rejected the human stem cells, they still recovered:
"When we implanted the human cells into mice that were paralyzed, they got up and started walking a couple of weeks later, and they completely recovered over the next several months."
"We've been studying mouse stem cells for a long time," adds study co-leader Thomas Lane, immunologist from the University of Utah, "but we never saw the clinical improvement that occurred with the human cells that Dr. Loring's lab provided."
Implanted human stem cells prompted creation of regulatory T cells
While current MS therapies focus on suppressing the attack on the immune system, which removes myelin from nerve fibers, they are not entirely effective and carry side effects with them.
Prof. Loring and her team have been looking for alternative therapies using human pluripotent stem cells - cells that are able to transform into any of the cell types in the body.
Mice crippled by an autoimmune condition similar to MS were able to walk and even run after being injected with human stem cells.
She explains that what they observed in the mice after such cells were injected into their damaged spinal cords was a transformation:
"Tom called me up and said, 'You're not going to believe this.' He sent me a video, and it showed the mice running around the cages. I said, 'Are you sure these are the same mice?'''
Because the mice were able to continue walking after their bodies rejected the human stem cells a week after implantation, the team says this suggests the human stem cells were secreting certain proteins that had a long-lasting effect on halting the progression of MS in the mice.
First author Ron Coleman, a TSRI graduate student in Prof. Loring's lab, explains that "once the human stem cells kick that first domino, the cells can be removed and the process will go on because they've initiated a cascade of events."
Through their work, the team was able to show that the implanted human stem cells prompted the creation of a type of white blood cell called regulatory T cells, which shut down autoimmune responses at the end of an inflammation.
The stem cells also released proteins that triggered cells to "re-myelinate" the nerve cells that had been stripped.
More research needed for treatment in humans
Building on their findings, Prof. Loring and her team are aiming to pinpoint the specific proteins that the human precursor cells release. They explain that a class of proteins called transforming growth factor beta - or TGF-B - is quite promising, as other studies have shown they are involved in creating regulatory T cells.
If they are able to identify which proteins played a role in the recovery of the mice, they may be able to create MS treatments that do not involve the use of human stem cells.
"Once we identify the factors that are responsible for healing, we could make a drug out of them," explains Prof. Loring.
Speaking with Medical News Today, Prof. Loring further expanded on their upcoming research:
"Our goal is to develop an effective human therapy based on our remarkable results in mice. Right now, we can't predict exactly what that therapy will look like - it won't necessarily involve stem cells themselves, but may be a biologic or a small molecule that we identify when we learn more about how the stem cells promote clinical recovery in mice."
She explains that understanding how the human neural precursor cells are effective in mice will lead them to the creation of therapies in humans.
Written by Marie Ellis
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