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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1755-1761.
Prepublished online as a Blood First Edition Paper on May 19, 2005; DOI 10.1182/blood-2005-04-1496.
 Previous Article | Next Article 
Submitted April 15, 2005
Accepted May 10, 2005
Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T cell anergy
Emanuela Zappia, Simona Casazza, Enrico Pedemonte, Federica Benvenuto, Ivan Bonanni, Ezio Gerdoni, Debora Giunti, Antonella Ceravolo, Francesco Cazzanti, Francesco Frassoni, Gianluigi Mancardi, and Antonio Uccelli*
Neuroimmunology Unit, Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy
Neuroimmunology Unit, Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy; Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy
Department of Haematology, San Martino Hospital, Genoa, Italy
* Corresponding author; email: auccelli{at}neurologia.unige.it.
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 106 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.
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