Mesenchymal stem cells: A new strategy for immunosuppression and tissue repair

Yufang Shi, Gangzheng Hu, Juanjuan Su, Wenzhao Li, Qing Chen, Peishun Shou, Chunliang Xu, Xiaodong Chen, Yin Huang, Zhexin Zhu, Xin Huang, Xiaoyan Han, Ningxia Xie, Guangwen Ren

Research output: Contribution to journalReview article

328 Scopus citations

Abstract

Mesenchymal stem cells (MSCs) have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immunosuppressive in vitro and in vivo. Our recent studies have shown that un-stimulated MSCs are indeed incapable of immunosuppression; they become potently immunosuppressive upon stimulation with the supernatant of activated lymphocytes, or with combinations of IFN-γ with TNF-α, IL-1α or IL-1Β. This observation revealed that under certain circumstances, inflammatory cytokines can actually become immunosuppressive. We showed that there is a species variation in the mechanisms of MSC-mediated immunosuppression: immunosuppression by cytokine-primed mouse MSCs is mediated by nitric oxide (NO), whereas immunosuppression by cytokine-primed human MSCs is executed through indoleamine 2, 3-dioxygenase (IDO). Additionally, upon stimulation with the inflammatory cytokines, both mouse and human MSCs secrete several leukocyte chemokines that apparently serve to attract immune cells into the proximity with MSCs, where NO or IDO is predicted to be most active. Therefore, immunosuppression by inflammatory cytokine-stimulated MSCs occurs via the concerted action of chemokines and immune-inhibitory NO or IDO produced by MSCs. Thus, our results provide novel information about the mechanisms of MSC-mediated immunosuppression and for better application of MSCs in treating tissue injuries induced by immune responses.

Original languageEnglish (US)
Pages (from-to)510-518
Number of pages9
JournalCell Research
Volume20
Issue number5
DOIs
StatePublished - May 1 2010
Externally publishedYes

Keywords

  • Immune diseases
  • Immunosuppression
  • MSCs
  • Tissue repair

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Shi, Y., Hu, G., Su, J., Li, W., Chen, Q., Shou, P., Xu, C., Chen, X., Huang, Y., Zhu, Z., Huang, X., Han, X., Xie, N., & Ren, G. (2010). Mesenchymal stem cells: A new strategy for immunosuppression and tissue repair. Cell Research, 20(5), 510-518. https://doi.org/10.1038/cr.2010.44