We have reported that transplanted human mesenchymal stem/stromal cells (hMSCs) into central nervous system (CNS) suppressed neuronal damage on ischemia and spinal cord injury. While the hMSCs might decrease the inflammation by the modulation of microglial cells through a cell-cell communication, it is still unclear how hMSCs responded in the CNS parenchyma after the transplantation. The purpose of present study is to estimate the responses of hMSCs during CNS diseases. Culturing hMSCs were exposed condition media of mouse hippocampal homogenate which obtained from 1day after transient forebrain ischemia (ischemic brain condition medium: ibCM) to mimic hippocampal state of brain. Then, the cells were surveyed the transcriptome in comparison with non-ischemic hippocampal homogenate (brain condition medium: bCM). The hMSCs exposed by ibCM increased 98 genes >2-fold more and decreased 78 genes <2-fold more to compare with those by bCM. The top category of gene ontology included several chemokines such as CCL2 (MCP-1). Exposing the ibCM from different region of the brain, MCP-1 was increased in the media after hippocampal ibCM, but not cortical and cerebellar ibCM by ELISA. Moreover, gene expression of CCL2 were increased by the application of recombinant mouse IL-1β or TNFα in a dose-dependent manner, but not IFNγ, IL-4, IL-13 and IL-10. Then, the hMSCs were exposed ibCM in IL-1α/β and TNFα knockout (KO) mice. The increased MCP-1 with ibCM of wild-type mice was suppressed by the ibCM in IL-1 and TNFα KO mice. Co-application of IL-1β and TNFα further increased CCL2 expression on hMSCs. These results suggest that enhancing of the MCP-1 in hMSCs might be regulated by pro-inflammatory cytokines.(COI: NO)