The effect of pro-inflammatory cytokines on immunophenotype,differentiation capacity and immunomodulatory functions of human mesenchymal stem cells |
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| Institution: | 1. Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran;2. Department of Regenerative Biomedicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;3. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;4. Department of Developmental Biology, University of Science and Culture, Academic Center for Education, Culture and Research, Tehran, Iran;1. Alexander B. Osborn Hematopoietic Malignancy and Transplantation Program of the Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, Morgantown, WV;2. Protea Bioscience, Morgantown, WV;3. Department of Physiology & Pharmacology, West Virginia University School of Medicine, Morgantown, WV;4. Department of Neurobiology and Anatomy, West Virginia University School of Medicine, Morgantown, WV;5. Center for Basic and Translational Stroke Research, West Virginia University School of Medicine, Morgantown, WV;6. Center for Neuroscience, West Virginia University School of Medicine, Morgantown, WV;7. Department of Microbiology, Immunology and Cell Biology, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, Morganstown, WV;1. Discipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Galway, Ireland;2. Regenerative Medicine Institute (REMEDI), School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland;3. Orbsen Therapeutics, National University of Ireland, Galway, Galway, Ireland;4. CÚRAM, SFI Research Centre for Medical Devices, National University of Ireland Galway, Galway, Ireland |
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| Abstract: | 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. |
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| Keywords: | Mesenchymal stem cell CD45+ MSC Pro-inflammatory cytokine TGF-β Th17 cell MSC-mediated immunomodulation |
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