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Int Immunopharmacol. 2017 Jun;47:59-69. doi: 10.1016/j.intimp.2017.03.016. Epub 2017 Mar 30.

Human adipose tissue-derived mesenchymal stem cells in rheumatoid arthritis: Regulatory effects on peripheral blood mononuclear cells activation.

Author information

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.

KEYWORDS:

Adipose tissue-derived mesenchymal stem cells; Inflammation; Peripheral blood mononuclear cells; Rheumatoid arthritis; T helper 17 cells

PMID:
28364628
DOI:
10.1016/j.intimp.2017.03.016
[Indexed for MEDLINE]

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