title: Therapeutic efficacy of cord blood-derived mesenchymal stromal cells for the prevention of acute graft-versus-host disease in a xenogenic mouse model.
abstract: Human mesenchymal stromal cells (MSCs) have been successfully utilized for the treatment of refractory graft-versus-host disease (GvHD). Despite the large number of in vitro and in vivo models developed for clarifying their immunomodulatory properties, the mechanism of action of MSCs remains elusive and their efficacy controversial. Here, we tested the ability of cord blood-derived MSCs to alleviate the symptoms of GvHD induced by the injection of human peripheral blood mononuclear cells into NOD/SCID/γc(-) mice. In this in vivo xeno-GvHD model, we demonstrate that a single MSC injection is able to inhibit GvHD in terms of clinical signs and related mortality. We also show that in this model MSCs act by both immunomodulating T-cells and fostering recovery after irradiation. The translational impact of these findings could provide a reliable preclinical model for studying the efficacy, dosage, and time of administration of human MSCs for the prevention of acute GvHD.
authors.affiliation: CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Gregoire-Gauthier
authors.forename: Silvia
authors.initials: S
authors.lastname: Selleri
authors.forename: François
authors.initials: F
authors.lastname: Fontaine
authors.forename: Mame Massar
authors.initials: MM
authors.lastname: Dieng
authors.forename: Natalie
authors.initials: N
authors.lastname: Patey
authors.forename: Geneviève
authors.initials: G
authors.lastname: Despars
authors.forename: Christian M
authors.initials: CM
authors.lastname: Beauséjour
authors.forename: Elie
authors.initials: E
authors.lastname: Haddad
mesh_terms: D000208:Acute Disease; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000502:physiology; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D005312:Fetal Blood; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D056747:Immunomodulation; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011833:Radiation Injuries, Experimental / Q000517:prevention & control; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology / Q000637:transplantation; D014183:Transplantation, Heterologous; D015431:Weight Loss / Q000528:radiation effects
chemical_list: D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human