Ectoderm-Derived Frontal Bone Mesenchymal Stem Cells Promote Traumatic Brain Injury Recovery by Alleviating Neuroinflammation and Glutamate Excitotoxicity

Abstract

Traumatic brain injury (TBI) leads to cell and tissue impairment, as well as functional deficits. Stem cells promote structural and functional recovery and thus are considered as a promising therapy for various nerve injuries. Here, we aimed to investigate the role of ectoderm-derived frontal bone mesenchymal stem cells (FbMSCs) in promoting cerebral repair and functional recovery in a murine TBI model. FbMSCs showed fibroblast like morphology and osteogenic differentiation capacity. FbMSCs were CD105, CD29 positive and CD45, CD31 negative. Different from mesoderm-derived MSCs, FbMSCs highly expressed ectoderm-specific transcription factor Tfap2β and growth factor FGF1. FbMSC application significantly ameliorated the behavioral deficits of TBI mice and promoted neural regeneration. Immunofluorescence staining and qRT-PCR data revealed that microglial activation and astrocyte polarization to the A1 phenotype were suppressed by FbMSC application. In addition, FGF1 secreted from FbMSCs enhanced glutamate transportation by astrocytes and alleviated the cytotoxic effect of excessive glutamate on neurons. Therefore, MSCs with characteristics of FbMSCs might be good candidates for TBI therapy.