A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells

被引：270

作者：

Chabannes, Dominique

Hill, Marcelo

Merieau, Emmanuel

Rossignol, Julien

Brion, Regis

Soulillou, Jean Paul

Anegon, Ignacio

Cuturi, Maria Cristina

机构：

[1] CHU Nantes, ITERT, INSERM, U643, F-44093 Nantes, France

[2] Univ Nantes, Fac Med, Nantes, France

来源：

BLOOD | 2007年 / 110卷 / 10期

关键词：

D O I：

10.1182/blood-2007-02-075481

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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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收藏

页码：3691 / 3694

页数：4

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