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

<jats:p>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<jats:italic>.</jats:italic>Intra-articular SM-MSC injection ameliorated the clinical and histological severity of arthritis. Decrease in tumor necrosis factor-<jats:italic>α</jats:italic>, interferon-<jats:italic>γ</jats:italic>, 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<jats:sup>+</jats:sup>CXCR5<jats:sup>+</jats:sup>FoxP3<jats:sup>+</jats:sup>follicular Treg cells increased in the spleens of SM-MSC-treated mice. Regulatory B cell analysis showed that CD21<jats:sup>hi</jats:sup>CD23<jats:sup>hi</jats:sup>transitional 2 cells, CD23<jats:sup>low</jats:sup>CD21<jats:sup>hi</jats:sup>marginal zone cells, and CD19<jats:sup>+</jats:sup>CD5<jats:sup>+</jats:sup>CD1d<jats:sup>+</jats:sup>IL-10<jats:sup>+</jats:sup>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.</jats:p>