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Mouse study highlights brain stem cells as a potential personalized treatment for progressive MS

Background: Neural stem cells can reduce brain and spinal cord inflammation in animal models of MS

Macrophages, called “eater” cells of the immune system, are known to destroy bacteria and abnormal cells. Specialized macrophages, named microglia, are found widespread throughout the brain and spinal cord – in progressive MS, microglia become activated, causing prolonged inflammation throughout the brain and spinal cord and damaging nerve cells.

Recent research efforts have been devoted to treating the inflammation found in progressive MS using stem cell therapies. Stem cells are a unique group of cells that can develop into virtually any cell type found within the body. Particularly, neural stem cells (NSCs) – stem cells that develop into nerve cells – have been shown to improve central nervous system (CNS) inflammation in animal models of MS. Translating these findings into clinic, however, has proven difficult, because stem cells are found in the embryo, and are therefore not largely abundant. There’s an added risk that once the NSCs are transplanted into a human, their body will recognize the NSCs as foreign, and trigger an immune response for their elimination.

A research team led by Dr. Stefano Pluchino at University of Cambridge sought to discover how NSC transplantation influences chronic MS using a mouse model of the disease. The group published their findings in Cell Stem Cell.

The Study: Studying mice with chronic MS-like disease to find out whether iNSC transplantation is beneficial

As a solution to the low abundance and high rate of rejection of NSCs, induced neural stem cells (iNSCs) – generated by “reprogramming” adult skin cells into neural stem cells –have emerged. These can be directly generated by the patient’s own skin cells, which lessens the risk of an immune response, and means they can be made in large quantities.

To discover whether iNSC transplantation would be therapeutic in a mouse model of MS, the authors had to do just that: transplant iNSCs reprogrammed from adult skin cells into more than 175 mice with MS-like disease.

Results: iNSC transplantation improves inflammation and nerve damage in mouse model of MS

The research team first found that mice with chronic MS-like disease produced higher levels of succinate, a molecule that tells microglia and macrophages to cause inflammation in the cerebrospinal fluid (CSF) surrounding the brain and spinal cord. Transplanting NSCs and iNSCs into mice with MS-like disease not only lowered the levels of succinate present in the CSF. This stem cell transplantation lowered the amount of inflammation, and minimized nerve damage, within the mice CNS.

Comment: In an animal model of chronic MS, iNSCs act in reducing the disease burden by lowering the succinate found in the CSF. This in turn, does not trigger macrophages and microglia to cause inflammation, and nerve damage in these mice is lower as a result. Because iNSCs can be made from an adult’s own skin, they are highly personalized and offer an attractive treatment for inflammatory neurological diseases like MS. However, studies transplanting iNSCs into individuals with MS must be performed before we can decisively say that stem cell transplantation benefits progressive MS patients.

Source:

Peruzzotti-Jametti I et al. (2018) Macrophage-derived extracellular succinate licenses neural stem cells to suppress chronic neuroinflammation. Cell Stem Cell. 22: 355-68.

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