Intra-Articular Injection of Human Synovial Membrane-Derived Mesenchymal Stem Cells in Murine Collagen-Induced Arthritis: Assessment of Immunomodulatory Capacity In Vivo

Minglu Yan; Xin Liu; Qiujie Dang; He Huang; Fan Yang; Yang Li

doi:10.1155/2017/9198328

Intra-Articular Injection of Human Synovial Membrane-Derived Mesenchymal Stem Cells in Murine Collagen-Induced Arthritis: Assessment of Immunomodulatory Capacity In Vivo

Stem Cells Int. 2017:2017:9198328. doi: 10.1155/2017/9198328. Epub 2017 Jun 21.

Authors

Minglu Yan¹, Xin Liu¹, Qiujie Dang¹, He Huang¹, Fan Yang¹, Yang Li¹

Affiliation

¹ Department of Rheumatology and Immunology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150000, China.

Abstract

The aim of this study was to evaluate the efficacy of human synovial membrane-derived MSCs (SM-MSCs) in murine collagen-induced arthritis (CIA). Male mice (age 7-9 weeks) were injected intra-articularly with SM-MSCs obtained from patients with osteoarthritis, on days 28, 32, and 38 after bovine type II collagen immunization. The efficacy of SM-MSCs in CIA was evaluated clinically and histologically. Cytokine profile analyses were performed by real-time polymerase chain reaction and multiplex analyses. Splenic helper T (Th) cell and regulatory B cell subsets were analyzed by flow cytometry. Intra-articular SM-MSC injection ameliorated the clinical and histological severity of arthritis. Decrease in tumor necrosis factor-α, interferon-γ, and interleukin- (IL-) 17A and increase in IL-10 production were observed after SM-MSC treatment. Flow cytometry showed that Th1 and Th17 cells decreased, whereas Th2, regulatory T (Treg), and PD-1⁺CXCR5⁺FoxP3⁺ follicular Treg cells increased in the spleens of SM-MSC-treated mice. Regulatory B cell analysis showed that CD21^hiCD23^hi transitional 2 cells, CD23^lowCD21^hi marginal zone cells, and CD19⁺CD5⁺CD1d⁺IL-10⁺ regulatory B cells increased following SM-MSC treatment. Our results demonstrated that SM-MSCs injected in inflamed joints in CIA had a therapeutic effect and could prevent arthritis development and suppress immune responses via immunoregulatory cell expansion.