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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 21, 2007 Accepted July 25, 2007 A role for heme oxygenase - 1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells Dominique Chabannes*, Marcelo Hill, Emmanuel Merieau, Julien Rossignol, Regis Brion, Jean Paul Soulillou, Ignacio Anegon, and Maria Cristina Cuturi INSERM, U643, Nantes, France CHU Nantes, Institut de Transplantation et de Recherche en Transplantation, ITERT, Nantes, France Faculte de Medecine, Universite de Nantes, Nantes, France * Corresponding author; email: dominiquechabannes{at}nantes.inserm.fr. 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, here we tested the hypothesis that HO-1 could also 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 both HO-1 or iNOS totally reversed the protective activity of MSCs, inducing graft rejection. Adult human MSCs also expressed HO-1 and 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: A. Moreau, M. Hill, P. Thebault, J. Y. Deschamps, E. Chiffoleau, C. Chauveau, P. Moullier, I. Anegon, B. Alliot-Licht, and M. C. Cuturi Tolerogenic dendritic cells actively inhibit T cells through heme oxygenase-1 in rodents and in nonhuman primates FASEB J, September 1, 2009; 23(9): 3070 - 3077. [Abstract] [Full Text] [PDF] T. M. Brusko Mesenchymal Stem Cells: A Potential Border Patrol for Transplanted Islets? Diabetes, August 1, 2009; 58(8): 1728 - 1729. [Full Text] [PDF] Y. Ding, D. Xu, G. Feng, A. Bushell, R. J. Muschel, and K. J. Wood Mesenchymal Stem Cells Prevent the Rejection of Fully Allogenic Islet Grafts by the Immunosuppressive Activity of Matrix Metalloproteinase-2 and -9 Diabetes, August 1, 2009; 58(8): 1797 - 1806. [Abstract] [Full Text] [PDF] D. Mougiakakos, C. C. Johansson, and R. Kiessling Response:Resistance of naturally occurring regulatory T cells toward oxidative stress: possible link with intracellular catecholamine content and implications for cancer therapy Blood, July 9, 2009; 114(2): 488 - 489. [Full Text] [PDF] F. Casiraghi, N. Azzollini, P. Cassis, B. Imberti, M. Morigi, D. Cugini, R. A. Cavinato, M. Todeschini, S. Solini, A. Sonzogni, et al. Pretransplant Infusion of Mesenchymal Stem Cells Prolongs the Survival of a Semiallogeneic Heart Transplant through the Generation of Regulatory T Cells J. Immunol., September 15, 2008; 181(6): 3933 - 3946. [Abstract] [Full Text] [PDF] 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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