All 11 animals, which have a version of MS, showed a rapid reduction in functional deficits.
Analysis showed that the disease remained on course unless the molecules injected were of a certain size; that is, the molecular weight ranged between 50 and 100 kiloDaltons.
Research by others and results of their own work indicated hepatocyte growth factor, which is secreted by mesenchymal stem cells, was a likely instigator.
The scientists injected animals with 50 or 100 nanograms of the growth factor every other day for five days. The level of signaling molecules that promote inflammation decreased while the level of signaling molecules that counter inflammation increased. Neural cells grew and nerves laid bare by MS were rewrapped with myelin. The 100-nanogram injections appeared to provide slightly better recovery.
To test the system further, researchers tied up cell-surface receptors, in this case cMet receptors that are known to work with the growth factor.
When they jammed the receptors with a function-blocking cMet antibody, neither the mesenchymal stem cell medium nor the hepatocyte growth factor injections had any effect on the disease. In another test, injections of an anti-hepatocyte growth factor also blocked recovery.
The researchers will continue their studies, to determine if they can screen mesenchymal stem cells for those that produce the higher amounts of hepatocyte growth factor needed for effective treatment. That could lead to a more precise cell therapy.
"Could we now take away the mesenchymal stem cells and treat only with hepatocyte growth factor?" Miller asked. "We've shown we can do that in an animal but it's not clear if we can do that in a patient."
They also plan to test whether other factors may be used to stimulate the cMet receptors and induce recovery.
|Contact: Jessica Studeny|
Case Western Reserve University