title: Phylogenetic distinction of iNOS and IDO function in mesenchymal stem cell-mediated immunosuppression in mammalian species.
abstract: Mammalian mesenchymal stem cells (MSCs) have been shown to be strongly immunosuppressive in both animal disease models and human clinical trials. We have reported that the key molecule mediating immunosuppression by MSCs is species dependent: indoleamine 2,3-dioxygenase (IDO) in human and inducible nitric oxide synthase (iNOS) in mouse. In the present study, we isolated MSCs from several mammalian species, each of a different genus, and investigated the involvement of IDO and iNOS during MSC-mediated immunosuppression. The characterization of MSCs from different species was by adherence to tissue culture plastic, morphology, specific marker expression, and differentiation potential. On the basis of the inducibility of IDO and iNOS by inflammatory cytokines in MSCs, the tested mammalian species fall into two distinct groups: IDO utilizers and iNOS utilizers. MSCs from monkey, pig, and human employ IDO to suppress immune responses, whereas MSCs from mouse, rat, rabbit, and hamster utilize iNOS. Interestingly, based on the limited number of species tested, the iNOS-utilizing species all belong to the phylogenetic clade, Glires. Although the evolutionary significance of this divergence is not known, we believe that this study provides critical guidance for choosing appropriate animal models for preclinical studies of MSCs.
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, 225 South Chongqing Road, Shanghai 200025, China.
authors.forename: J
authors.initials: J
authors.lastname: Su
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, 225 South Chongqing Road, Shanghai 200025, China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
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, 225 South Chongqing Road, Shanghai 200025, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
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, 225 South Chongqing Road, Shanghai 200025, China.
authors.forename: W
authors.initials: W
authors.lastname: Li
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, 225 South Chongqing Road, Shanghai 200025, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
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, 225 South Chongqing Road, Shanghai 200025, China.
authors.forename: K
authors.initials: K
authors.lastname: Cao
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, 225 South Chongqing Road, Shanghai 200025, China.
authors.forename: G
authors.initials: G
authors.lastname: Cao
authors.affiliation: Child Health Institute of New Jersey, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 89 French Street, NJ 08901, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
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, 225 South Chongqing Road, Shanghai 200025, China.
authors.forename: F
authors.initials: F
authors.lastname: Li
authors.affiliation: Child Health Institute of New Jersey, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 89 French Street, NJ 08901, USA.
authors.forename: A I
authors.initials: AI
authors.lastname: Roberts
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, 225 South Chongqing Road, Shanghai 200025, China.
authors.forename: H
authors.initials: H
authors.lastname: Kang
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, 225 South Chongqing Road, Shanghai 200025, China.
authors.forename: P
authors.initials: P
authors.lastname: Yu
authors.affiliation: Child Health Institute of New Jersey, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 89 French Street, NJ 08901, USA.
authors.forename: G
authors.initials: G
authors.lastname: Ren
authors.affiliation: Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
authors.forename: W
authors.initials: W
authors.lastname: Ji
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, 225 South Chongqing Road, Shanghai 200025, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1] 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, 225 South Chongqing Road, Shanghai 200025, China [2] Child Health Institute of New Jersey, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 89 French Street, NJ 08901, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D006224:Cricetinae; D004195:Disease Models, Animal; D000882:Haplorhini; D006801:Humans; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology*; D010802:Phylogeny; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D052247:Nitric Oxide Synthase Type II