Reprogramming Skin Cells Shows Promise in Multiple Sclerosis

Induced neural stem cells may hold the key to reducing multiple sclerosis-related central nervous system damage.

A recent study published by Cell Stem Cell suggest that skin cells reprogrammed into stem cells may help repair multiple sclerosis (MS)-related damage.

The approach of transplanting newly created brain stem cells into the central nervous system was found to reduce inflammation and reverse damage in mice models of MS.

The findings represent progress towards developing personalized stem cell therapies based on skin cells for central nervous system (CNS) diseases, according to the authors.

“Our mouse study suggests that using a patient’s reprogrammed cells could provide a route to personalised [sic] treatment of chronic inflammatory diseases, including progressive forms of MS,” said lead author Stefano Pluchino, MD, PhD.

Macrophages are a significant player in immune-mediated MS damage. In progressive MS, microglia—macrophages found in the brain and spinal cord—attack the CNS, which results in inflammation and nerve cell damage, according to the authors.

The researchers previously discovered that transplanted neural stem cells (NSCs) are able to resolve inflammation and promote CNS repair; however, the authors noted that the therapy would require NSCs from embryos, thus preventing large scale production. This approach may also trigger an attack against NSCs.

A potential solution to these problems would be to use skin cells reprogrammed to become neural stem cells, known as induced neural stem cells (iNSCs). These cells would not likely spark an immune reaction since they originated within the patient.

The authors demonstrated that iNSCs may be able to repair MS damage to the CNS.

In mice models, chronic MS resulted in increased levels of the succinate metabolite, which signals macrophages and microglia to cause inflammation in the cerebrospinal fluid and peripheral blood, according to the study.

When NSCs and iNSCs were transplanted into the cerebrospinal fluid, levels of succinate dropped. This was found to reprogram the macrophages and microglia to reduce inflammation, according to the study.

The reduction in inflammation was also found to reduce damage to the brain and spinal cord.

If proven in humans with MS, iNSC transplants may become an effective method to prevent CNS damage and associated disability.

“This is particularly promising as these cells should be more readily obtainable than conventional neural stem cells and would not carry the risk of an adverse immune response,” Dr Pluchino said.