Placenta-derived mesenchymal stem cells have an immunomodulatory effect that can control acute graft-versus-host disease in mice

Acta Haematol. 2013;129(4):197-206. doi: 10.1159/000345267. Epub 2012 Dec 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Interferon-gamma