Transcriptome analysis reveals that the injection of mesenchymal stem cells remodels extracellular matrix and complement components of the brain through PI3K/AKT/FOXO1 signaling pathway in a neuroinflammation mouse model

Neurological disorders are often accompanied by neuroinflammatory responses. Our previous research indicated that mesenchymal stem cells (MSCs) suppressed neuroinflammation in the brain. The mechanism of action remains not fully understood. In this study, we analyzed the impact of injected MSCs on the transcriptome in the brains of neuroinflammatory mouse model (NIM) with bioinformatical methods and conducted experimental validation with qPCR and Western blot. The results showed that the expression of extracellular matrix components changed, and the complement cascade was activated in the NIM brains. Injection of MSCs reversed the expression of ECM components and inhibited complement activation. MSCs may promote the improvement of neuronal synaptic function and alter the infiltration of immune cells into the brain. MSCs regulated the PI3K/AKT/Foxo1 signaling pathway. These findings will be very helpful for the development of MSCs-based therapy and the treatment of neuroinflammation-related diseases.