title: Mesenchymal stem cells: a new strategy for immunosuppression and tissue repair.
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-gamma with TNF-alpha, IL-1alpha or IL-1beta. 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.
authors.affiliation: Key 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 200025, China. shiyufang2@gmail.com
authors.forename: Yufang
authors.initials: Y
authors.lastname: Shi
authors.forename: Gangzheng
authors.initials: G
authors.lastname: Hu
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Su
authors.forename: Wenzhao
authors.initials: W
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.forename: Peishun
authors.initials: P
authors.lastname: Shou
authors.forename: Chunliang
authors.initials: C
authors.lastname: Xu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Chen
authors.forename: Yin
authors.initials: Y
authors.lastname: Huang
authors.forename: Zhexin
authors.initials: Z
authors.lastname: Zhu
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Han
authors.forename: Ningxia
authors.initials: N
authors.lastname: Xie
authors.forename: Guangwen
authors.initials: G
authors.lastname: Ren
mesh_terms: D000818:Animals; D006801:Humans; D007154:Immune System Diseases / Q000276:immunology / Q000628:therapy*; D007165:Immunosuppression Therapy / Q000379:methods* / Q000639:trends; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D014945:Wound Healing