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Mesenchymal Stem Cell Migration and Tissue Repair
Open AccessArticle

Combination Therapy of Mesenchymal Stromal Cells and Interleukin-4 Attenuates Rheumatoid Arthritis in a Collagen-Induced Murine Model

1
Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
2
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
3
Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
4
Department of Medical Biochemistry, National Research Center, Cairo 11562, Egypt
*
Author to whom correspondence should be addressed.
Cells 2019, 8(8), 823; https://doi.org/10.3390/cells8080823
Received: 14 June 2019 / Revised: 22 July 2019 / Accepted: 23 July 2019 / Published: 3 August 2019
(This article belongs to the Special Issue Advances in Stem Cells and Regenerative Medicine)
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Abstract

Rheumatoid arthritis (RA) is a disease of the joints that causes decreased quality of life. Mesenchymal stromal cells (MSCs) have immunosuppressive properties, with possible use in the treatment of RA. Similarly, interleukin (IL)-4 has been shown as a potential RA treatment. However, their combination has not been explored before. Therefore, this study aimed to investigate the effect of a combination therapy of MSCs and IL-4 in the treatment of RA, using a murine collagen-induced arthritis (CIA) model. Arthritis was induced in Balb/c mice by two intradermal injections of type II collagen (CII), at days 0 and 21. CIA mice were randomly assigned to four groups; group I received an intravenous injection of mouse bone marrow-derived MSCs, while group II received an intraperitoneal injection of IL-4. Group III received a combined treatment of MSC and IL-4, while group IV served as a CIA diseased control group receiving phosphate buffer saline (PBS). A fifth group of healthy mice served as the normal healthy control. To assess changes induced by different treatments, levels of RA-associated inflammatory cytokines and biomarkers were measured in the serum, knee joints, and synovial tissue, using ELISA and Real Time-qPCR. Histopathological features of knee joints were analyzed for all groups. Results showed that combined MSC and IL-4 treatment alleviated signs of synovitis in CIA mice, reverting to the values of healthy controls. This was evident by the decrease in the levels of rheumatic factor (RF), C-reactive protein (CRP) and anti-nuclear antibodies (ANA) by 64, 80, and 71%, respectively, compared to the diseased group. Moreover, tumor necrosis factor-alpha (TNF- α) and monocyte chemoattractant protein-1 (MCP-1) levels decreased by 63 and 68%, respectively. Similarly, our gene expression data showed improvement in mice receiving combined therapy compared to other groups receiving single treatment, where cartilage oligomeric matrix protein (Comp), tissue inhibitor metalloproteinase-1 (Timp1), matrix metalloproteinase1 (Mmp-1), and IL-1 receptor (Il-1r) gene expression levels decreased by 75, 70, and 78%, respectively. Collectively, treatment with a combined therapy of MSC and IL-4 might have an efficient therapeutic effect on arthritis. Thus, further studies are needed to assess the potential of different MSC populations in conjugation with IL-4 in the treatment of experimental arthritis. View Full-Text
Keywords: rheumatoid arthritis; auto-inflammatory disease; cytokines; IL-4; mesenchymal stem cells; mouse model; collagen-induced arthritis; inflammatory mediators rheumatoid arthritis; auto-inflammatory disease; cytokines; IL-4; mesenchymal stem cells; mouse model; collagen-induced arthritis; inflammatory mediators
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Haikal, S.M.; Abdeltawab, N.F.; Rashed, L.A.; Abd El-Galil, T.I.; Elmalt, H.A.; Amin, M.A. Combination Therapy of Mesenchymal Stromal Cells and Interleukin-4 Attenuates Rheumatoid Arthritis in a Collagen-Induced Murine Model. Cells 2019, 8, 823.

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