1. A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells
- Author
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Dominique Chabannes, Maria-Cristina Cuturi, Julien Rossignol, Emmanuel Merieau, Régis Brion, Jean-Paul Soulillou, Marcelo Hill, and Ignacio Anegon
- Subjects
Oxygenase ,Transplantation, Heterotopic ,Metalloporphyrins ,Immunology ,Protoporphyrins ,Biology ,Pharmacology ,Biochemistry ,chemistry.chemical_compound ,In vivo ,Immune Tolerance ,Animals ,Humans ,Heme ,Cells, Cultured ,Mesenchymal stem cell ,Graft Survival ,Mesenchymal Stem Cells ,Cell Biology ,Hematology ,In vitro ,Rats ,Transplantation ,Nitric oxide synthase ,Heme oxygenase ,chemistry ,biology.protein ,Heart Transplantation ,Transplantation Tolerance ,Heme Oxygenase-1 - 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.
- Published
- 2007