title: Comparative analysis of human mesenchymal stem cells from fetal-bone marrow, adipose tissue, and Warton's jelly as sources of cell immunomodulatory therapy.
abstract: To characterize different tissue MSCs as sources of cell immunomodulatory therapy. Examined the effects of IFN-γ on WJ-MSC and their immunomodulatory function characteristics. We compared human fetal bone marrow (F-BM), adipose tissue (AT), and Warton's Jelly-derived MSCs (WJ-MSCs) for surface antigen expression, differentiation ability, proliferation capacity, clonality, tolerance for aging, gene expression, and whether IFN-γ affected WJ-MSC gene expression, as determined by real time quantitative PCR. Fifteen geneswere examined. We further assess WJ-MSCs-mediated immunomodulatory on peripheral blood mononuclear, stimulated by PHA, IL-2 and CD3Ab after 5 days of co-cultured in a 5:1 ratio (PBMC:MSCs). Examined the effect of WJ-MSCs on the Th1, Th2, Th17 cytokines production and Treg augument. MSCs from different tissues have similar levels of cell surface antigen expression and differentiation ability, while F-BM-MSCs and WJ-MSC had higher rates of cell proliferation and clonality than AD-MSCs. All 15 genes were expressed at similar levels in WJ-MSCs and AD-MSCs (P > 0.05). 9 genes were upregulated in WJ-MSCFor F-MSC, including IL-6, CXCL9, CXCL10, CXCL11, ICAM-1, IDO1, HLA-G5, SDF1A, and NOTCH were down expression, but VCAM-1 was lower expressionin WJ-MSCS. After IFN-γ treatment, 7 genes were upregulated in WJ-MSC, including chemokine ligands CXCL9, CXCL10 and CXCL11, and the adhesion protein VCAM1and ICAM1. Additionally, immunosuppressive factors, such as HLA-G and IDO were both increased. When cocultured with peripheral blood mononuclear, WJ-MSCs showed an immunosuppressive function by inhibit the proliferative response of Th1 and Th17 but augment Th2 and Treg. Primed WJ-MSCs by IFNγ caused a greater reduction in IFNγ and TNFα than untreated WJ-MSCs, also the effect on augument in Treg and inhibit Th17 (P < 0.01). Our results demonstrate that primitive F-BM-MSCs and WJ-MSCs have biological advantages as compared to adult cells, WJ-MSCs have a gene expression pattern similar to AT-MSCs but not F-BM MSCs, and that inflammatory stimuli regulate gene expression in WJ-MSCs. WJ-MSC showed the immunosuppressive function in co-cultured system with PBMC, and IFNγ can promoted the immunosuppressive function.
authors.affiliation: a Shengjing Hospital; China Medical University ; Shenyang , PR China.
authors.forename: Qiushi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: a Shengjing Hospital; China Medical University ; Shenyang , PR China.
authors.forename: Qiaoni
authors.initials: Q
authors.lastname: Yang
authors.affiliation: a Shengjing Hospital; China Medical University ; Shenyang , PR China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: a Shengjing Hospital; China Medical University ; Shenyang , PR China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Tong
authors.affiliation: a Shengjing Hospital; China Medical University ; Shenyang , PR China.
authors.forename: Liangyan
authors.initials: L
authors.lastname: Ma
authors.affiliation: a Shengjing Hospital; China Medical University ; Shenyang , PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: b Department of Immunology ; School of Basic Medical Science; China Medical University ; Shenyang , PR China.
authors.forename: Fengping
authors.initials: F
authors.lastname: Shan
authors.affiliation: b Department of Immunology ; School of Basic Medical Science; China Medical University ; Shenyang , PR China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Meng
authors.affiliation: a Shengjing Hospital; China Medical University ; Shenyang , PR China.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000954:Antigens, Surface / Q000032:analysis; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D049109:Cell Proliferation; D018920:Coculture Techniques; D020869:Gene Expression Profiling; D006801:Humans; D056747:Immunomodulation; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D000954:Antigens, Surface; D007371:Interferon-gamma
keywords: Wharton's jelly; adipose tissue; fetal bone marrow; gene expression; mesenchymal stem cells