The effect of pro-inflammatory cytokines on immunophenotype, differentiation capacity and immunomodulatory functions of human mesenchymal stem cells.
Mesenchymal stem cells (MSCs), as cells with potential clinical utilities, have demonstrated preferential incorporation into inflammation sites. Immunophenotype and immunomodulatory functions of MSCs could alter by inflamed-microenvironments due to the local pro-inflammatory cytokine milieu. A major cellular mediator with specific function in promoting inflammation and pathogenicity of autoimmunity are IL-17-producing T helper 17 (Th17) cells that polarize in inflamed sites in the presence of pro-inflammatory cytokines such as Interleukin-1β (IL-1β), IL-6 and IL-23. Since MSCs are promising candidate for cell-based therapeutic strategies in inflammatory and autoimmune diseases, Th17 cell polarizing factors may alter MSCs phenotype and function. In this study, human bone-marrow-derived MSCs (BM-MSC) and adipose tissue-derived MSCs (AD-MSC) were cultured with or without IL-1β, IL-6 and IL-23 as pro-inflammatory cytokines. The surface markers and their differentiation capacity were measured in cytokine-untreated and cytokine-treated MSCs. MSCs-mediated immunomodulation was analyzed by their regulatory effects on mixed lymphocyte reaction (MLR) and the level of IL-10, TGF-β, IL-4, IFN-γ and TNF-α production as immunomodulatory cytokines. Pro-inflammatory cytokines showed no effect on MSCs morphology, immunophenotype and co-stimulatory molecules except up-regulation of CD45. Adipogenic and osteogenic differentiation capacity increased in CD45+ MSCs. Moreover, cytokine-treated MSCs preserved the suppressive ability of allogeneic T cell proliferation and produced higher level of TGF-β and lower level of IL-4. We concluded pro-inflammatory cytokines up-regulate the efficacy of MSCs in cell-based therapy of degenerative, inflammatory and autoimmune disorders.
Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Arash
A
Pourgholaminejad
Department of Regenerative Biomedicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Nasser
N
Aghdami
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, Academic Center for Education, Culture and Research, Tehran, Iran.
Hossein
H
Baharvand
Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: moazzeni@modares.ac.ir.
Seyed Mohammad
SM
Moazzeni
D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D056747:Immunomodulation / Q000276:immunology*; D016130:Immunophenotyping / Q000379:methods; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D015415:Biomarkers; D016207:Cytokines; D017493:Leukocyte Common Antigens
CD45+ MSC; MSC-mediated immunomodulation; Mesenchymal stem cell; Pro-inflammatory cytokine; TGF-β; Th17 cell