Species Variation in the Mechanisms of Mesenchymal Stem Cell-Mediated Immunosuppression
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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The effective functionality of MSCs in immune regulation relies on their initial activation by a pro-inflammatory microenvironment.
“The effective functionality of MSCs in immune regulation relies on their initial activation by a pro-inflammatory microenvironment.”
From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [18]
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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
- ORCID
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- 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
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- 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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