AMD3100 modulates the secretome responses of human Mesenchymal Stromal Cells but not their inhibitory effect on T cell proliferation

AMD3100 (Plerixafor) is being utilized in clinic for the mobilization of Hematopoietic Stem Cell (HSCs) from bone marrow into peripheral blood to facilitate peripheral blood sourced HSC transplantation. It is important to identify the immunomodulatory role of AMD3100 in bone marrow niche. We have investigated the effect of AMD3100 on culture expanded human bone marrow derived Mesenchymal Stem/Stromal Cells (BM MSCs) which are non-hematopoietic cells of the marrow niche. AMD3100 does not modulate the metabolic activity of BM MSCs. However, multiplex secretome analysis demonstrated that AMD3100 alters the specific innate secretory molecules of BM MSCs. AMD3100 also amplifies the chemokine secretion of MSCs upon stimulation with IFNγ and TNFα. Flow cytometry analysis identified that AMD3100 augments IFNγ and TNFα mediated induction of the immunosuppressive enzyme Indoleamine 2, 3 Dioxygenase (IDO) in human BM MSCs. Coculture functional analysis of human BM MSCs with Peripheral Blood Mononuclear Cells (PBMCs) has demonstrated that BM MSCs dose dependently inhibits the T cell proliferation and exogenous addition of AMD3100 did not modulate this inhibition. In contrast, secretory analysis showed that AMD3100 modulates the secretory responses of BM MSCs and activated PBMC cocultures. These results suggest that AMD3100 modulates the immunomodulatory effect of BM MSCs and alters the soluble milieu of marrow niche.