Multiple sclerosis (MS) is a debilitating neurodegenerative disease that results from an immune system attack on myelin sheaths, the protective outer coatings of axons that are essential for proper communication between neurons. Impairment of myelin and oligodendrocytes, the cells that produce myelin, causes widespread impairments in brain function.

Human mesenchymal stem cells (MSCs), which are derived from bone marrow, appear particularly promising for the treatment of MS because they can modulate both the immune system and neural cell responses. These cells have emerged as a promising approach for stem cell–based therapies for several neurological disorders, because they seem to possess factors that promote repair.

In animal models of MS, treatment with MSCs not only lessens the immune system's attack on myelin and oligodendrocytes, but also leads to myelin repair. A research team led by Robert Miller at Case Western Reserve University (Cleveland, OH) has now shown that medium conditioned with the secretions of human MSCs is sufficient to induce the beneficial effects in a mouse model of MS (Nat. Neurosci. published online 20 May 2012; doi:10.1038/nn.3109). The medium itself is able to reduce functional deficits and promote the development of new oligodendrocytes and neurons.

Assuming that something secreted by these cells was responsible for the beneficial effect, the researchers next systematically tested the components of the medium to isolate the powerful substance. They finally identified hepatocyte growth factor (HGF) and its receptor cMet as being crucial to the MSC-stimulated recovery. When the mice were injected with HGF alone, they showed the same improvement in symptoms compared with controls. HGF appears to both block the destructive autoimmune response and repair neuronal damage. Similarly, blocking HGF or cMet prevented the recovery from taking place in the diseased mice.

The improvements that resulted from the HGF treatment were vastly superior to those induced in humans with MS by current treatments, which suppress the immune system from attacking nerve cells but do nothing to repair existing damage. Fortunately, there are several clinical trials testing the efficacy of MSC treatment of MS. This new research could lead scientists to improve the efficacy of this treatment approach by selectively treating patients with cells that produce high levels of HGF. Alternatively, HGF may prove to be an effective treatment on its own, bypassing the complications that can arise with stem cell–based treatments.