Investigators will examine whether proteins called “chemokines” can direct certain stem cells in the brain to sites where myelin, the sheath surrounding nerve cell axons in the brain and spinal cord, has been damaged in the autoimmune disease multiple sclerosis (MS). If so, the stem cells, once mature, could repair the damaged myelin.
In MS, immune cells mistake myelin as foreign, and cross the blood-brain-barrier to attack it, producing inflammation. Most current MS therapies, therefore, act to suppress this inflammatory response. An alternative approach may be even more effective, according to researchers, based on recent evidence that chemokines (protein compounds on the surface of cells) can guide cells to their destination. Chemokines are known to direct immune cells to sites of inflammation, and recent studies in the animal model of MS, called experimental autoimmune encephalomyelitis (EAE), indicate that levels of chemokines and their receptors are increased during acute exacerbations of symptoms in EAE. Surprisingly, the researchers have found, chemokine receptors occur in neurons, in glial cells that interact with neurons to produce the myelin sheath, and in the stem cells that are the progenitors of neurons and glial cells. These findings suggest that chemokines can guide these cells to specific destinations as well.
The researchers hypothesize, therefore, that chemokines at sites of myelin damage might be able to direct stem cells that destined to become glial cells to these damaged sites. If so, these cells then could help repair the myelin damage. They will test this hypothesis in the EAE animal model of MS by defining the signaling of progenitor glial cells in two ways. They will inject and transplant into the EAE mice glial progenitor cells grown in tissue culture, and they will ask how chemokines act on the endogenous population of glial progenitor cells residing in the mouse brain. They also will determine whether, once signaled, these endogenous progenitor cells migrate to the sites of myelin inflammation.
Significance: By defining the role of chemokine signaling in the animal model of MS,and seeing whether chemokines can direct glial stem cells to sites of inflammatory damage of myelin to repair this damage, the research may lay the groundwork for developing an entirely new therapeutic approach to autoimmune MS.