Cited by 598Mesenchymal stem cell researchHematopoietic Stem Cell TransplantationPluripotent Stem Cells Research

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

Ren, Guangwen, Su, Juanjuan, Zhang, Liying, Zhao, Xin, Ling, Weifang, L'huillie, Andrew, Zhang, Jimin, Lu, Yongqing +5 more·2009·Stem Cells

Abstract

Bone 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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Crossref · 10.1002/stem.118

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Authors
Ren, G., Su, J., Zhang, L., Zhao, X., Ling, W., L'huillie, A., Zhang, J., Lu, Y., Roberts, A. I., Ji, W., Zhang, H., Rabson, A. B., & Shi, Y.
Affiliations
  • University of Medicine and Dentistry of New Jersey (US)
  • Shanghai Jiao Tong University (CN)
  • Kunming Institute of Zoology (CN)
Corresponding author
Shi, Yufang
Venue
Stem Cells
Published
2009-05-07
Volume
27
Issue
8
Pages
1954-1962
ISSN
  • 1066-5099 (ISSN-L)
  • 1549-4918
OpenAlex
W2034706779
Cited by
597
References
42
Citations by year
2026: 7 · 2025: 11 · 2024: 11 · 2023: 31 · 2022: 25 · 2021: 48 · 2020: 39 · 2019: 44 · 2018: 38 · 2017: 41 · 2016: 49 · 2015: 45 · 2014: 52 · 2013: 47 · 2012: 39
FWCI
17.15
Type
journal article
Language
en
Open access
closed
Locations
  • Stem Cells (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • New Jersey Commission on Science and Technology (NJCST-2042-014-84)
  • Chinese Academy of Sciences, National Institutes of Health (AI057596, AI50222)
  • National Space Biomedical Research Institute (IIH00405)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords
mesenchymal stem cells, immunosuppression, species differences, indoleamine 2,3-dioxygenase, inducible nitric oxide synthase, nitric oxide, inflammatory cytokines, immune regulation, bone marrow-derived stem cells, immune disorders
MeSH terms
Animals, Humans, Immune Tolerance, Macaca mulatta, Nitric Oxide, Species Specificity, Cytokines, Mesenchymal Stem Cell Transplantation, Indoleamine-Pyrrole 2,3,-Dioxygenase, Mice, Nitric Oxide Synthase Type II, Mesenchymal Stem Cells

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