Cell therapy with mesenchymal stromal cells (MSCs) is the focus of intensive investigation. Several
clinical trials, including large-scale placebo-controlled phase III clinical trials, are currently underway evaluating
the therapeutic potential of autologous and allogeneic MSCs for treatment of catastrophic inflammatory
diseases, including steroid-refractory graft-versus-host disease (GvHD), multiple sclerosis (MS) and Crohn’s
disease. MSCs are also being investigated as carriers of anti-cancer biotherapeutics. We here review recent
developments in our understanding of the immunosuppressive properties of MSCs. We firstly discuss the
effects of ex vivo culture conditions on the phenotype and functions of MSCs. Secondly, we summarize the
immune functions suppressed by MSCs with a focus on T cell, B cell, natural killer cell and dendritic cell
functions. Thirdly, we discuss newly identified pathways responsible for the immunosuppressive activity of
MSCs, including the expression of heme-oxygenase (HO)-1, the secretion of galectins, CCL2 antagonism, T
regulatory cell (Treg) cross-talk and production of TNF-α stimulated gene/protein-6 (TSG-6). Finally, we review
the literature on the molecular pathways governing MSC homing and discuss recent clinical data on the use of
MSCs for treatment of GvHD, MS and Crohn’s disease.
Keywords: Cancer, GVHD, immunosuppression, mesenchymal, multiple sclerosis, stem cell, stromal, Treg.
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