title: Bone marrow mesenchymal stem cells suppress lymphocyte proliferation in vitro but fail to prevent graft-versus-host disease in mice.
abstract: Several reports have suggested that mesenchymal stem cells (MSCs) could exert a potent immunosuppressive effect in vitro, and thus may have a therapeutic potential for T cell-dependent pathologies. We aimed to establish whether MSCs could be used to control graft-vs-host disease (GVHD), a major cause of morbidity and mortality after allogeneic hemopoietic stem cell transplantation. From C57BL/6 and BALB/c mouse bone marrow cells, we purified and expanded MSCs characterized by the lack of expression of CD45 and CD11b molecules, their typical spindle-shaped morphology, together with their ability to differentiate into osteogenic, chondrogenic, and adipogenic cells. These MSCs suppressed alloantigen-induced T cell proliferation in vitro in a dose-dependent manner, independently of their MHC haplotype. However, when MSCs were added to a bone marrow transplant at a MSCs:T cells ratio that provided a strong inhibition of the allogeneic responses in vitro, they yielded no clinical benefit on the incidence or severity of GVHD. The absence of clinical effect was not due to MSC rejection because they still could be detected in grafted animals, but rather to an absence of suppressive effect on donor T cell division in vivo. Thus, in these murine models, experimental data do not support a significant immunosuppressive effect of MSCs in vivo for the treatment of GVHD.
authors.affiliation: Biologie et Thérapeutique des Pathologies Immunitaires Université Pierre et Marie Curie/Centre National de la Recherche Scientifique Unité Mixte de Recherche 7087, Paris, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Sudres
authors.forename: Françoise
authors.initials: F
authors.lastname: Norol
authors.forename: Aurélie
authors.initials: A
authors.lastname: Trenado
authors.forename: Sylvie
authors.initials: S
authors.lastname: Grégoire
authors.forename: Frédéric
authors.initials: F
authors.lastname: Charlotte
authors.forename: Béatrice
authors.initials: B
authors.lastname: Levacher
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lataillade
authors.forename: Philippe
authors.initials: P
authors.lastname: Bourin
authors.forename: Xavier
authors.initials: X
authors.lastname: Holy
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vernant
authors.forename: David
authors.initials: D
authors.lastname: Klatzmann
authors.forename: José L
authors.initials: JL
authors.lastname: Cohen
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000473:pathology*; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011828:Radiation Chimera; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism