Background: Mesenchymal stem cell-derived neural progenitor cell (MSC-NP) therapy is an experimental approach to treat multiple sclerosis. The influence of MSC-NPs on microglial activation was investigated. Methods: Microglia were stimulated in the presence of MSC-NP-conditioned media, and proinflammatory or proregenerative marker expression was assessed by quantitative PCR and ELISA. Results: Microglia stimulated in the presence of MSC-NP-conditioned media displayed reduced expression of proinflammatory markers including CCL2, increased expression of proregenerative markers and reduced phagocytic activity. The paracrine effects of MSC-NPs from multiple donors correlated with TGF-β3 gene expression and was reversed by TGF-β signaling inhibition. Conclusion: MSC-NPs promote beneficial microglial polarization through secreted factors. This study suggests that microglia are a potential therapeutic target of MSC-NP cell therapy.
Keywords: CCL2; MSC-NP; TGF-β; cell therapy; mesenchymal stem cell; microglia; multiple sclerosis.
Multiple sclerosis (MS) is a chronic inflammatory disease of the brain and spinal cord that leads to neuronal damage and neurological disability. A novel cell therapy has been developed aiming to slow or reverse neurological disability in patients with MS. The treatment approach utilizes bone marrow cells called mesenchymal stem cell-derived neural progenitors (MSC-NPs) that are injected into the spinal fluid of the patient. Microglia are an innate immune cell in the brain known to contribute to MS disease progression. This study explores whether microglia might be a therapeutic target of MSC-NP therapy. We found that MSC-NPs inhibited the inflammatory activation of microglia and increased proregenerative markers in microglia. These effects were mediated by the factors secreted by MSC-NPs, possibly including a secreted protein called TGF-β. Overall, this study highlights a potential therapeutic mechanism of MSC-NP therapy in MS.