Document Detail

A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells.
MedLine Citation:
PMID:  17684157     Owner:  NLM     Status:  MEDLINE    
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.
Dominique Chabannes; Marcelo Hill; Emmanuel Merieau; Julien Rossignol; Régis Brion; Jean Paul Soulillou; Ignacio Anegon; Maria Cristina Cuturi
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Publication Detail:
Type:  Journal Article     Date:  2007-08-07
Journal Detail:
Title:  Blood     Volume:  110     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-11-06     Completed Date:  2008-01-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3691-4     Citation Subset:  AIM; IM    
Institut National de la Santé et de la Recherche Médicale (INSERM), U643, Nantes, France.
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MeSH Terms
Cells, Cultured
Graft Survival
Heart Transplantation / immunology
Heme Oxygenase-1 / physiology*
Immune Tolerance / genetics*
Mesenchymal Stem Cells / drug effects,  immunology,  physiology*
Metalloporphyrins / pharmacology
Protoporphyrins / pharmacology
Transplantation Tolerance / immunology
Transplantation, Heterotopic / immunology
Reg. No./Substance:
0/Metalloporphyrins; 0/Protoporphyrins; 14325-05-4/tin protoporphyrin IX; EC Oxygenase-1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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