Stem cell research & therapy

mTOR inhibition improves the immunomodulatory properties of human bone marrow mesenchymal stem cells by inducing COX-2 and PGE

PMID 29287601


Bone marrow mesenchymal stem cells (MSCs) are promising candidates for the treatment of various inflammatory disorders due to their profound immunomodulatory properties. However, the immunosuppressive capacity of MSCs needs activation by an inflammatory microenvironment, which may negatively impact the therapeutic effect because of increased immunogenicity. Here we explore the role of mammalian target of rapamycin (mTOR) signaling on the immunosuppressive capacity of MSCs, and its impact on immunogenicity in the inflammatory microenvironment. Human bone marrow MSCs were cocultured with activated human peripheral blood mononuclear cells, CD4 Inhibition of mTOR signaling using rapamycin enhanced the immunosuppressive functions of MSCs, while prolonged exposure to rapamycin did not. The enhancement of the immunosuppressive function was independent of the inflammatory microenvironment, and occurred mainly through the upregulation of COX-2 and prostaglandin-E These results reveal that the mTOR signaling pathway regulates MSC immunobiology, and short-term exposure to rapamycin could be a novel approach to improve the MSC-based therapeutic effect.