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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.


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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 Soulillou13, 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.


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