Mouse Flk-1+Sca-1- mesenchymal stem cells: functional plasticity in vitro and immunoregulation in vivo

Transplantation. 2014 Mar 15;97(5):509-17. doi: 10.1097/01.TP.0000442775.46133.38.

Abstract

Objectives: Mesenchymal stem cells (MSCs) represent a powerful tool in regenerative medicine because of their differentiation and migration capacities. Moreover, the immunomodulatory ability of MSCs may be used to develop therapies for the treatment of autoimmune diseases.

Methods: In this study, we isolated Flk-1Sca-1 MSCs from bone marrow (bMSCs). Next, we studied their biological characteristics and immunologic functions. We also investigated their effects on graft-versus-host disease (GVHD) associated with allogeneic bone marrow transplantation in mice.

Results: Flk-1Sca-1 bMSCs were able to differentiate into fat and cartilage cells, indicating that the isolated cells had stem cell properties. They could also suppress alloantigen-induced T cell proliferation in vitro in a dose-dependent manner. Infusion of bMSCs into allogeneic bone marrow-transplanted mice alleviated the lethal GVHD that occurred in control recipient mice. There was significantly lower mortality among the recipients of the Flk-1Sca-1 bMSCs that also ameliorated the clinical symptoms and GVHD histopathology. Beneficial effects on GVHD by Flk-1Sca-1 bMSCs were also observed when MSCs were engineered to express anti-inflammatory cytokines IL-4 and IL-10 and decrease expression of proinflammatory cytokines IFN-γ, TNF-α, and IL-2.

Conclusion: Flk-1Sca-1 bMSCs have stem cell properties and can efficiently ameliorate the GVHD associated with allogeneic bone marrow transplantation in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / metabolism*
  • Bone Marrow Transplantation
  • Cell Differentiation / physiology*
  • Cell Movement / physiology*
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / metabolism
  • Female
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / pathology
  • Graft vs Host Disease / prevention & control
  • Immunomodulation / physiology*
  • In Vitro Techniques
  • Membrane Proteins / metabolism*
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • T-Lymphocytes / pathology
  • Time Factors
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*

Substances

  • Antigens, Ly
  • Cytokines
  • Ly6a protein, mouse
  • Membrane Proteins
  • Vascular Endothelial Growth Factor Receptor-2