title: Mechanisms of immune modulation by mesenchymal stromal cells and clinical translation.
abstract: 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.
authors: Institut du Cancer de Montreal, Centre de Recherche du Centre Hospitalier de l'Universite de Montreal, Faculte de Pharmacie, 1560 rue Sherbrooke E. Montreal, Quebec, H2L 4M1, Canada. john.stagg@umontreal.ca
authors: J
authors: J
authors: Stagg
authors: J
authors: J
authors: Galipeau
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D063646:Carcinogenesis / Q000473:pathology; D002465:Cell Movement; D016207:Cytokines / Q000502:physiology; D006801:Humans; D007154:Immune System Diseases / Q000628:therapy; D007113:Immunity, Innate; D007165:Immunosuppression Therapy / Q000379:methods*; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D059630:Mesenchymal Stem Cells / Q000473:pathology / Q000502:physiology*; D009369:Neoplasms / Q000209:etiology
chemical_list: D016207:Cytokines