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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. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-04-1496v1 106/5/1755    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zappia, E. Articles by Uccelli, A. Search for Related Content PubMed PubMed Citation Articles by Zappia, E. Articles by Uccelli, A. Related Collections Immunobiology Immunotherapy Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY 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 From the Neuroimmunology Unit, Department of Neurosciences, Ophthalmology and Genetics, and the Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; and the Department of Haematology, San Martino Hospital, Genoa, Italy. We studied the immunoregulatory features of murine mesenchymal stem cells (MSCs) in vitro and in vivo. MSCs inhibited T-cell receptor (TCR)-dependent and -independent proliferation but did not induce apoptosis on T cells. Such inhibition was paired with a decreased interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha production and was partially reversed by interleukin-2 (IL-2). Thus, we used MSCs to treat myelin oligodendrocyte glycoprotein (MOG)35-55-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). MSC administration before disease onset strikingly ameliorated EAE. The therapeutic scheme was effective when MSCs were administered at disease onset and at the peak of disease but not after disease stabilization. Central nervous system (CNS) pathology showed decreased inflammatory infiltrates and demyelination in mice that received transplants of MSCs. T-cell response to MOG and mitogens from MSC-treated mice was inhibited and restored by IL-2 administration. Upon MSC transfection with the enhanced green fluorescent protein (eGFP), eGFP+ 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. (Blood. 2005; 106:1755-1761) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Finding a less toxic stem cell therapy for multiple sclerosis Richard K. Burt Blood 2005 106: 1514-1515. [Full Text] [PDF] This article has been cited by other articles: R. Atoui, D. Shum-Tim, and R. C.J. Chiu Myocardial regenerative therapy: immunologic basis for the potential "universal donor cells". Ann. Thorac. Surg., July 1, 2008; 86(1): 327 - 334. [Abstract] [Full Text] [PDF] R. Abdi, P. Fiorina, C. N. Adra, M. Atkinson, and M. H. 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