Species Variation in the Mechanisms of Mesenchymal Stem Cell-Mediated Immunosuppression

Stem Cells - Tập 27 Số 8 - Trang 1954-1962 - 2009
Guangwen Ren1, Juanjuan Su2,3, Liying Zhang1, Xin Zhao1, Baoli Hu1, Andrew L'huillie1, Jimin Zhang1, Yujie Lu2,3, Arthur I. Roberts1, Weizhi Ji3, Huatang Zhang3, Arnold B. Rabson4,1, Yufang Shi1,2,3
1Department of Molecular Genetics, Microbiology and Immunology, Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey, USA
2Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, Shanghai, China
3Kunming Primate Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, People's Republic of China
4Child Health Institute of New Jersey, Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey, USA

Tóm tắt

AbstractBone marrow-derived mesenchymal stem cells (MSCs) hold great promise for treating immune disorders because of their immunoregulatory capacity, but the mechanism remains controversial. As we show here, the mechanism of MSC-mediated immunosuppression varies among different species. Immunosuppression by human- or monkey-derived MSCs is mediated by indoleamine 2,3-dioxygenase (IDO), whereas mouse MSCs utilize nitric oxide, under the same culture conditions. When the expression of IDO and inducible nitric oxide synthase (iNOS) were examined in human and mouse MSCs after stimulation with their respective inflammatory cytokines, we found that human MSCs expressed extremely high levels of IDO, and very low levels of iNOS, whereas mouse MSCs expressed abundant iNOS and very little IDO. Immunosuppression by human MSCs was not intrinsic, but was induced by inflammatory cytokines and was chemokine-dependent, as it is in mouse. These findings provide critical information about the immunosuppression of MSCs and for better application of MSCs in treating immune disorders.Disclosure of potential conflicts of interest is found at the end of this article.

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Stem Cells

Tập 27 Số 8

1954-1962

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