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, Régis Brion, Jean Paul Soulillou, Ignacio Anegon, Maria Cristina Cuturi

Research output: Contribution to journalArticlepeer-review

283 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3691-3694
Number of pages4
JournalBlood
Volume110
Issue number10
DOIs
StatePublished - Nov 15 2007

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