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Blood, 15 November 2007, Vol. 110, No. 10, pp. 3691-3694. Prepublished online as a Blood First Edition Paper on August 7, 2007; DOI 10.1182/blood-2007-02-075481. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2007-02-075481v1 110/10/3691    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 Chabannes, D. Articles by Cuturi, M. C. Search for Related Content PubMed PubMed Citation Articles by Chabannes, D. Articles by Cuturi, M. C. Related Collections Stem Cells in Hematology Brief Reports Hematopoiesis Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Brief Report A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells Dominique Chabannes1,2, Marcelo Hill1, Emmanuel Merieau1, Julien Rossignol1, Régis Brion1, Jean Paul Soulillou1,3, Ignacio Anegon1, and Maria Cristina Cuturi1 1 Institut National de la Santé et de la Recherche Médicale (INSERM), U643, Nantes; 2 Institut de Transplantation et de Recherche en Transplantation (ITERT), Centre Hospitalier Universitaire (CHU) Nantes; and 3 Faculté de Médecine, Université de Nantes, Nantes, France Mesenchymal stem cells (MSCs) display immunomodulatory properties mediated by various factors, including inducible nitric oxide synthase (iNOS). Since heme oxygenase-1 (HO-1) is a potent immunosuppressive enzyme, we tested the hypothesis that HO-1 could mediate the immunosuppressive effects of MSCs. We generated adult rat MSCs that inhibited T-cell proliferation in vitro. These MSCs expressed both HO-1 and iNOS. In vitro, whereas neither HO-1 nor iNOS inhibition alone could interfere with the immunosuppressive properties of rat MSCs, simultaneous inhibition of both enzymes restored T-cell proliferation. In vivo, injection of MSCs significantly delayed heart allograft rejection, and inhibition of either HO-1 or iNOS totally reversed the protective activity of MSCs, inducing rejection. Adult human MSCs also expressed HO-1; in these cells, HO-1 inhibition was sufficient to completely block their immunosuppressive capacity. In conclusion, we show, for the first time, that HO-1 mediates the immunosuppressive properties of rat and human MSCs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. J. Weiss, J. K. Kolls, L. A. Ortiz, A. Panoskaltsis-Mortari, and D. J. Prockop Stem Cells and Cell Therapies in Lung Biology and Lung Diseases Proceedings of the ATS, July 15, 2008; 5(5): 637 - 667. [Full Text] [PDF] 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. Sayegh Immunomodulation by Mesenchymal Stem Cells: A Potential Therapeutic Strategy for Type 1 Diabetes Diabetes, July 1, 2008; 57(7): 1759 - 1767. [Abstract] [Full Text] [PDF] N. G. Abraham and A. Kappas Pharmacological and Clinical Aspects of Heme Oxygenase Pharmacol. Rev., March 1, 2008; 60(1): 79 - 127. [Abstract] [Full Text] [PDF]

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