Microglia contribute to the pathogenesis of brain diseases by regulating of neuroinflammation. Thus, targeting of neuroinflammation triggered by activated microglia in brain diseases has become a promising curative strategy. Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been shown to have therapeutic effects, resulting from the regulation of inflammatory conditions in the brain. In this study, Gene expression pattern in rat BM-MSCs (rBM-MSCs) cocultured with lipopolysaccharide- (LPS-) stimulated primary rat microglia were investigated using microarray analysis and the functional relationships were evaluated through Ingenuity Pathway Analysis (IPA). The effects of rBM-MSC on LPS-stimulated microglia were also assessed using a reverse coculture system and the same transcriptomic analysis. In rBM-MSCs, 67 genes were differentially expressed, which were highly related with migration of cells, compared to control. The gene network was predicted using IPA and LPS-stimulated primary rat microglia increase the migration of rBM-MSCs was validated by experiments. Reversely, expression patterns of the transcriptome in LPS-stimulated primary rat microglia cocultured with rBM-MSCs were changed. Results showed that 64 genes were altered, which were highly related with inflammatory response, compared to absence of rBM-MSCs. In the same procedure with the aforementioned, the prediction of the gene network and experimental validation showed that rBM-MSCs decrease the inflammatory response of LPS-stimulated primary rat microglia. These indicate that LPS-stimulated microglia increase the migration of rBM-MSCs and that rBM-MSCs reduce the inflammatory activity in LPS-stimulated microglia. The results of this study show complex mechanisms underlying the interaction between rBM-MSCs and activated microglia and may be supportive for the advance of stem cell therapy for brain diseases. This study is based on a previously published report
