|
|
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.
Previous Article | Table of Contents | Next Article 
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.

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]
|
 |
|
|
|