Cleveland researchers find key to stem-cell therapy for MS patients: Discoveries

CLEVELAND, Ohio -- One of the most promising and exciting treatment avenues for multiple sclerosis is the use of a patient's own stem cells to try to stop -- or even repair -- some of the disease's brain tissue damage.

But injecting a patient with a dose of his or her own bone-marrow stem cells was actually a pretty crude method of treating the disease, because no one was quite sure how or why it worked. Last year, doctors at the Cleveland Clinic, University Hospitals Seidman Cancer Center and Case Western Reserve University began trying this for MS patients in a Phase 1 clinical trial after positive results were seen in mice.

Multiple sclerosis is an autoimmune disease in which the immune system attacks the myelin sheaths that surround and protect nerve cells. When myelin is damaged, the nerve cells are exposed and unable to do their job, which is sending signals to the brain and back. This results in the loss of motor skills, coordination and cognitive abilities.

Like many other researchers using stem cells, the local group didn't know exactly how their treatment worked, but they knew that when they gave these human mesenchymal stem cells, or MSCs, to mice with a mouse version of the disease, the mice got better.

Figuring out why the mice improved could help researchers see if the MSC injection will work well in a particular patient before the patient is injected, and possibly augment or improve the treatment as well.

In May, the research group at CWRU, headed up by neurosciences professor Robert Miller, discovered exactly what it is in the stem-cell soup that has a healing effect: a large molecule called hepatocyte growth factor, or HGF. The team published their results in Nature Neuroscience.

Miller's group knew that it could be the stem cells themselves, by coming in physical contact with the myelin damage, that were having a healing effect. Or it could be something the stem cells secreted into the surrounding liquid culture, or media, they were grown in, that was key. HGF is secreted by the stem cells, Miller said.

The team identified the HGF by first injecting only the liquid the stem cells were grown in, but not the stem cells themselves, into the mice they were studying. The mice got better, so the team knew whatever was helping was in the media.

Next, they isolated the small, medium and large molecules from the media and tried each size on the mice. Only the large-molecule treatment had the healing effect, meaning that whatever was helping was somewhere in that mix, Miller said.

"The molecule that jumped out at us was HGF," he said, because it is the right size, is made by MSCs, and in a couple of studies had been shown to be involved in myelin repair.

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Cleveland researchers find key to stem-cell therapy for MS patients: Discoveries