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Acta Haematol ; 129(4): 197-206, 2013.
Article in English | MEDLINE | ID: mdl-23257958

ABSTRACT

BACKGROUND AND AIMS: Immunomodulatory properties of mesenchymal stem cells (MSCs) have been applied to reduce the incidence of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). Among the various sources of MSCs that have immunomodulatory effects in vitro, only placenta-derived MSCs (PD-MSCs) have not been evaluated in an in vivo model of GVHD. In this study, we investigated the immunomodulatory properties of PD-MSCs in vitro and evaluated their clinical potential for controlling GVHD in an animal model. METHODS: A GVHD animal model was established by transplanting C57BL/6 donor bone marrow cells and spleen cells into lethally irradiated BALB/c recipient mice. To control GVHD, human PD-MSCs were transplanted into recipient mice (5 × 10(5) or 1 × 10(6) cells). RESULTS: PD-MSCs suppressed mitogen-stimulated T cell proliferation in vitro in a dose-dependent manner. Moreover, PD-MSCs inhibited cytokine secretion (interleukin-12, tumor necrosis factor-α and interferon-γ) of activated T cells. In vivo, the survival rate in the PD-MSC group (transplanted with 1 × 10(6) cells) was higher than that in the control group and histological scores were low in the PD-MSC group. CONCLUSION: We present the first evidence that human PD-MSCs can efficiently control GVHD in an HSCT in vivo model.


Subject(s)
Graft vs Host Disease/immunology , Graft vs Host Disease/prevention & control , Immunomodulation , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/immunology , Placenta/cytology , Animals , Bone Marrow Transplantation/immunology , Cell Differentiation , Disease Models, Animal , Female , G2 Phase , Graft vs Host Disease/mortality , Graft vs Host Disease/pathology , Humans , Interferon-gamma/metabolism , Interleukin-12/metabolism , Lymphocyte Activation/immunology , Mesenchymal Stem Cell Transplantation , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Pregnancy , Survival Rate , T-Lymphocytes/metabolism , Tumor Necrosis Factor-alpha/metabolism
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