Effect of mesenchymal stem cells on glial cells population in cuprizone induced demyelination model

Mesenchymal stem cells (MSCs) have a notable potential to modulate immune responses and protect the central nervous system (CNS), mostly by secreting factors that affect inflammation. MSCs have the ability to improve several autoimmune diseases in animal models including multiple sclerosis (MS). MS is a disease of the CNS among adult humans and it is characterized by demyelination, neuroinflammation and gliosis. In this study, we first induced chronic demyelination by cuprizone, followed by intraventricular injection of MSC. Our results showed that MSC significantly decreased microgliosis and astrocytosis by secreting cytokines that have neuroprotective activity including TGF-beta and CX3CL1. Also, downregulation of IL-1 beta and TNF-alpha as inflammatory chemokines was seen along with decreased astrocytes and microglia activation. Finally, these results showed that trophic factors secreted by MSC can increase oligodendrocyte population and remyelination rate by reducing pro-inflammatory factors. These findings demonstrate that MSC could decrease inflammation, gliosis and demyelination with neuroprotective and immunomodulating properties in chronic cuprizone demyelination model. Therefore MSC transplantation can be considered as a suitable approach for enhancing myelination and reducing inflammation in diseases such as MS.