Rasoul Baharlou1, Abbas Ahmadi-Vasmehjani2, Fatemeh Faraji1, Mohammad Reza Atashzar1, Mahshid Khoubyari3, Salma Ahi4, Saiedeh Erfanian5, Shadi-Sadat Navabi1. 1. Department of Immunology and Microbiology, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran. 2. Department of Immunology and Microbiology, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran. Electronic address: ahvasmehjani@gmail.com. 3. Department of Student Research Committee, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran. 4. Department of Internal Medicine, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran. 5. Research Center for Non-Communicable Diseases, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran.
Abstract
BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) are multipotent adult stem cells with immunomodulatory properties. The mechanisms by which MSCs inhibit the proliferation of pro-inflammatory T cells have not been fully elucidated yet. It is assumed that pro-inflammatory T-cells play an important role in the development of autoimmune diseases. We investigated the potential therapeutic effects of human adipose tissue derived (Ad)-MSCs on the peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients and healthy individuals, with a particular focus on Th17-associated cytokines. MATERIALS AND METHODS: PBMCs from RA patients and healthy donors were co-cultured with Ad-MSCs and HeLa with or without Phytohemagglutinin (PHA). Finally, IL-6, IL-17, IL-21, IL-23 and TGF-β levels were determined by ELISA and quantitative real-time RT-PCR on co-culture supernatants and PBMCs, respectively. RESULTS: In co-culture interaction, Ad-MSCs inhibited IL-17 secretion by PBMCs compared to unstimulated PBMCs cultured alone. In addition, IL-21 expressions in PBMCs of the patient group, and IL-17 and IL-21 in healthy group were inhibited by Ad-MSCs compared to PBMCs cultured alone. TGF-β expression in healthy individuals remarkably increased in both MSC-treated groups with and without PHA in comparison to PHA-stimulated and -unstimulated PBMCs. CONCLUSIONS: This study demonstrates that human Ad-MSCs act as key regulators of immune tolerance by inhibiting the inflammation. Therefore, they can be attractive candidates for immunomodulatory cell-based therapy in RA.
BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) are multipotent adult stem cells with immunomodulatory properties. The mechanisms by which MSCs inhibit the proliferation of pro-inflammatory T cells have not been fully elucidated yet. It is assumed that pro-inflammatory T-cells play an important role in the development of autoimmune diseases. We investigated the potential therapeutic effects of human adipose tissue derived (Ad)-MSCs on the peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients and healthy individuals, with a particular focus on Th17-associated cytokines. MATERIALS AND METHODS: PBMCs from RApatients and healthy donors were co-cultured with Ad-MSCs and HeLa with or without Phytohemagglutinin (PHA). Finally, IL-6, IL-17, IL-21, IL-23 and TGF-β levels were determined by ELISA and quantitative real-time RT-PCR on co-culture supernatants and PBMCs, respectively. RESULTS: In co-culture interaction, Ad-MSCs inhibited IL-17 secretion by PBMCs compared to unstimulated PBMCs cultured alone. In addition, IL-21 expressions in PBMCs of the patient group, and IL-17 and IL-21 in healthy group were inhibited by Ad-MSCs compared to PBMCs cultured alone. TGF-β expression in healthy individuals remarkably increased in both MSC-treated groups with and without PHA in comparison to PHA-stimulated and -unstimulated PBMCs. CONCLUSIONS: This study demonstrates that human Ad-MSCs act as key regulators of immune tolerance by inhibiting the inflammation. Therefore, they can be attractive candidates for immunomodulatory cell-based therapy in RA.