Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T cell anergy

  • Zappia E
  • Casazza S
  • Pedemonte E
 et al. 
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We studied the immunoregulatory features of murine mesenchymal stem cells (MSCs) in vitro ed in vivo. MSCs inhibited TCR dependent and independent proliferation but not induced apoptosis on T cells. Such inhibition was paired by a decreased IFN-gamma and TNF-alpha production and was partially reversed by IL-2. Thus, we utilized MSCs to treat MOG35-55 induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice. We injected intravenously 1 x 10(6) MSCs before disease onset (preventive protocol) and at different time points after disease occurrence (therapeutic protocol). MSCs administration before disease onset strikingly ameliorated EAE. The therapeutic scheme was effective when MSC were administered at disease onset and at the peak of disease but not after disease stabilization. CNS pathology showed decreased inflammatory infiltrates and demyelination in MSCs transplanted mice. T cell response to MOG and mitogens from MSCs treated mice was inhibited and restored by IL-2 administration. Upon MSC transfection with the enhanced Green Fluorescent Protein (eGFP), GFP+ cells were detected in the lymphoid organs of treated mice. These data suggest that the immunoregulatory properties of MSCs effectively interfere with the autoimmune attack in the course of EAE inducing an in vivo state of T cell unresponsiveness occurring within secondary lymphoid organs

Author-supplied keywords

  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Clonal Anergy
  • Clonal Anergy: immunology
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental
  • Encephalomyelitis, Autoimmune, Experimental: chemi
  • Encephalomyelitis, Autoimmune, Experimental: immun
  • Encephalomyelitis, Autoimmune, Experimental: preve
  • Glycoproteins
  • Green Fluorescent Proteins
  • Green Fluorescent Proteins: immunology
  • Interferon-gamma
  • Interferon-gamma: immunology
  • Interferon-gamma: metabolism
  • Interleukin-2
  • Interleukin-2: pharmacology
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stromal Cells
  • Mesenchymal Stromal Cells: immunology
  • Mice
  • Mice, Inbred C57BL
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell: immunology
  • Signal Transduction
  • Signal Transduction: immunology
  • T-Lymphocytes
  • T-Lymphocytes: drug effects
  • T-Lymphocytes: immunology
  • Tumor Necrosis Factor-alpha
  • Tumor Necrosis Factor-alpha: immunology

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  • E. Zappia

  • S. Casazza

  • E. Pedemonte

  • F. Benvenuto

  • I. Bonanni

  • E. Gerdoni

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