28 February 2018

Personalized approach

In multiple sclerosis, the body's immune system attacks its own tissues and damages myelin, a protein that forms the outer lining of nerves. This leads to a slowdown or complete cessation of the transmission of the nerve impulse. The clinical manifestations of multiple sclerosis depend on the location of the lesion. Macrophages that are part of the microglia of the brain and spinal cord are most actively involved in the autoimmune destruction of myelin.

Researchers from the University of Cambridge have proposed reprogramming skin cells into stem cells and transplanting them into the brain or spinal cord to repair damage caused by multiple sclerosis.

Previous work has proven that neural stem cell transplantation (NSC) reduces inflammation and restores the tissues of the central nervous system after injury. The cornerstone was the method of obtaining NSCs: embryonic stem cells were used in the study, but their widespread use is limited due to the lack of primary material. In addition, there is a risk that the body will perceive them as a foreign agent and destroy them through an immune reaction.

The solution to this problem was found in the use of induced stem cells, that is, cells obtained by reprogramming the somatic cells of the patient's body. In this case, the skin cells were reprogrammed into the NSC. The use of NSCs derived from their own cells excludes an immune response to them.

To confirm the hypothesis, experiments were conducted on mouse models of multiple sclerosis.

Researchers have found that with multiple sclerosis, the level of succinate, an anion (acid residue) of succinic acid, a low–molecular metabolite that activates microglial cells and causes chronic inflammation, increases in the cerebrospinal fluid.

NSCs injected directly into the cerebrospinal fluid interact with succinate: the latter binds to SUCNR1 receptors on the surface of the NSC. In response, the NSC begins to actively secrete prostaglandin E2, which reduces the amount of succinate. The provoking effect on macrophages weakens. There is a re-education of immune cells: "bad" macrophages turn into "good" ones. This leads to a decrease in inflammation and secondary damage to the brain and spinal cord.

Evidence of the effectiveness of NSCs obtained by reprogramming the body's own cells can give rise to personalized therapy of chronic inflammatory diseases of the central nervous system, including progressive forms of multiple sclerosis.

Article by L. Peruzzotti-Jametti et al. Macrophage-Derived Extracellular Succinate Licenses Neural Stem Cells to Suppress Chronic Neuroinflammation is published in the journal Cell Stem Cell.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Cambridge: Study in mice suggests personalized stem cell treatment may offer relief for progressive MS.

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