The online edition of Nature Neuroscience reports that researchers from the Case Western Reserve University School of Medicine have discovered that a substance within growth promoting human mesenchymal stem cells seems to spur restoration of nerves and their function in mice models with multiple sclerosis (MS).

Animals that were injected with hepatocyte growth factor were noted to have grown new neural cells and lower levels of inflammation. Most significantly, the researchers noted that the protective envelope of myelin, the myelin sheath, which surrounds the core of a nerve fiber and facilitates the transmission of nerve impulses, re-grew and covered lesions that were caused by MS.

Robert H. Miller, professor of neurosciences at the School of Medicine and vice president for research at Case Western Reserve University declared: “The importance of this work is we think we’ve identified the driver of the recovery.”

MS is caused by damage to the myelin sheath, the protective covering that surrounds nerve cells. The nerve damage is caused by inflammation, which occurs when the body’s own immune cells attacks the nervous systems located in areas of the brain, the optic nerve, and spinal cord. This damage can cause an interruption of the nerve signals, which results in loss of balance and coordination, cognitive ability, as well as in other functions and in time, these intermittent losses may become permanent.
In 2009, Caplan and Miller discovered that mice with MS injected with human mesenchymal stem cells recovered from the type of damage that was brought on by MS. A clinical trial is currently underway based on their research, whereby patients with MS are injected with their own stems cells.

During this trial, the team decided to first establish whether the presence of stem cells or other cells induce recovery. They injected a total of 11 animals with MS with the medium, in which mesenchymal stem cells that were taken from bone marrow grew, discovering that all animals displayed a rapid reduction in functional deficits. An analysis demonstrated that unless the injected molecules had a certain size or weight, i.e. between 50 and 100 kiloDaltons, the course of the disease remained unchanged.

Other research, as well as the team’s own studies, suggested that this was likely to be instigated by the hepatocyte growth factor, which is secreted by mesenchymal stem cells.

The team then injected the animals with either 50 or 100 nanograms of the growth factor on alternate days for a 5-day period and observed a decrease in the level of signaling molecules that promote inflammation, whilst the level of signaling molecules that oppose inflammation increased. The researchers noted a growth of neural cells, whilst nerves that were exposed because of MS were rewrapped with myelin. Recovery was marginally better in those mice that received the 100-nanogram injections compared with those receiving the 50-nanogram injections.

In a further test, the team tied up cell-surface receptors, such as cMet receptors, which are known to work with the growth factor. They noted after inhibiting the receptors function with a cMet antibody, that neither the hepatocyte growth factor injections nor the mesenchymal stem cell medium affected the disease. Another test also revealed that recovery was blocked by injections of an anti-hepatocyte growth factor.

The research continues in pursuit of establishing whether mesenchymal stem cells can be screened for those that produce the higher amounts of hepatocyte growth factor required for efficient treatment, as this could result in a more accurate cell therapy.

Miller asked:

“Could we now take away the mesenchymal stem cells and treat only with hepatocyte growth factor? We’ve shown we can do that in an animal but it’s not clear if we can do that in a patient.”

The team also wants to examine whether cMET receptors can also be stimulated by other factors and induce recovery.

Written By Petra Rattue