B7-H1 Promotes the Functional Effect of Human Gingiva-Derived Mesenchymal Stem Cells on Collagen-Induced Arthritis Murine Model.
Ontology highlight
ABSTRACT:
SUBMITTER: Wu W
PROVIDER: S-EPMC7646216 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BACKGROUND:Mesenchymal stem cells derived from gingiva (GMSCs) display profound immunomodulation properties in addition to self-renewal and multilineage differentiation capacities. Hydrogen sulfide (H2S) is not only an environmental pollutant, but also is an important biological gas transmitter in health and disease. METHODS:We used an in-vitro coculture system and a mouse colitis model to compare the immunomodulatory effects between control and H2S-deficient GMSCs. The flow cytometry analysis was used for T-cell apoptosis and T-helper 17 (Th17) and regulatory T (Treg) cell differentiation. RESULTS:We revealed that GMSCs exerted their immunomodulatory effect by inducing T-cell apoptosis, promoting Treg cell polarization, and inhibiting Th17 cell polarization in vitro. The levels of H2S regulated the immunomodulatory effect of GMSCs. Mechanically, H2S deficiency downregulated the expression of Fas in GMSCs, resulting in reduced secretion of monocyte chemotactic protein 1 (MCP-1), which in turn led to decreased T-cell migration to GMSCs mediated by MCP-1. Moreover, H2S deficiency downregulated the expression of Fas ligand (FasL) in GMSCs. The Fas/FasL coupling-induced T-cell apoptosis by GMSCs was attenuated in H2S-deficient GMSCs. Consistent with this, H2S-deficient GMSCs showed attenuated therapeutic effects on colitis in vivo, which could be restored by treatment with the H2S donor, NaHS. CONCLUSIONS:These findings showed that H2S was required to maintain immunomodulation of GMSCs, which was mediated by Fas/FasL coupling-induced T-cell apoptosis.
| S-EPMC5845196 | biostudies-literature
Project description:Current approaches offer no cures for rheumatoid arthritis (RA). Accumulating evidence has revealed that manipulation of bone marrow-derived mesenchymal stem cells (BM-MSCs) may have the potential to control or even prevent RA, but BM-MSC-based therapy faces many challenges, such as limited cell availability and reduced clinical feasibility. This study in mice with established collagen-induced arthritis (CIA) was undertaken to determine whether substitution of human gingiva-derived mesenchymal stem cells (G-MSCs) would significantly improve the therapeutic effects.CIA was induced in DBA/1J mice by immunization with type II collagen and Freund's complete adjuvant. G-MSCs were injected intravenously into the mice on day 14 after immunization. In some experiments, intraperitoneal injection of PC61 (anti-CD25 antibody) was used to deplete Treg cells in arthritic mice.Infusion of G-MSCs in DBA/1J mice with CIA significantly reduced the severity of arthritis, decreased the histopathology scores, and down-regulated the production of inflammatory cytokines (interferon-? and interleukin-17A). Infusion of G-MSCs also resulted in increased levels of CD4+CD39+FoxP3+ cells in arthritic mice. These increases were noted early after infusion in the spleens and lymph nodes, and later after infusion in the synovial fluid. The FoxP3+ Treg cells that were increased in frequency mainly consisted of Helios-negative cells. When Treg cells were depleted, infusion of G-MSCs partially interfered with the progression of CIA. Pretreatment of G-MSCs with a CD39 or CD73 inhibitor significantly reversed the protective effect of G-MSCs on CIA.The role of G-MSCs in controlling the development and severity of CIA mostly depends on CD39/CD73 signals and partially depends on the induction of CD4+CD39+FoxP3+ Treg cells. G-MSCs provide a promising approach for the treatment of autoimmune diseases.
| S-EPMC4364405 | biostudies-literature
Project description:Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory synovitis leading to joint destruction and systemic bone loss. The inflammation-induced bone loss is mediated by increased osteoclast formation and function. Current antirheumatic therapies primarily target suppression of inflammatory cascade with limited or no success in controlling progression of bone destruction. Mesenchymal stem cells (MSCs) by virtue of their tissue repair and immunomodulatory properties have shown promising results in various autoimmune and degenerative diseases. However, the role of MSCs in prevention of bone destruction in RA is not yet understood. In this study, we investigated the effect of adipose-derived MSCs (ASCs) on in vitro formation of bone-resorbing osteoclasts and pathological bone loss in the mouse collagen-induced arthritis (CIA) model of RA. We observed that ASCs significantly inhibited receptor activator of NF-?B ligand (RANKL)-induced osteoclastogenesis in both a contact-dependent and -independent manner. Additionally, ASCs inhibited RANKL-induced osteoclastogenesis in the presence of proinflammatory cytokines such as TNF-?, IL-17, and IL-1?. Furthermore, treatment with ASCs at the onset of CIA significantly reduced clinical symptoms and joint pathology. Interestingly, ASCs protected periarticular and systemic bone loss in CIA mice by maintaining trabecular bone structure. We further observed that treatment with ASCs reduced osteoclast precursors in bone marrow, resulting in decreased osteoclastogenesis. Moreover, ASCs suppressed autoimmune T cell responses and increased the percentages of peripheral regulatory T and B cells. Thus, we provide strong evidence that ASCs ameliorate inflammation-induced systemic bone loss in CIA mice by reducing osteoclast precursors and promoting immune tolerance.
| S-EPMC4654226 | biostudies-literature
Project description:Atherosclerosis is the major cause of cardiovascular diseases. Current evidences indicate that inflammation is involved in the pathogenesis of atherosclerosis. Human gingiva-derived mesenchymal stem cells (GMSC) have shown anti-inflammatory and immunomodulatory effects on autoimmune and inflammatory diseases. However, the function of GMSC in controlling atherosclerosis is far from clear. The present study is aimed to elucidate the role of GMSC in atherosclerosis, examining the inhibition of GMSC on macrophage foam cell formation, and further determining whether GMSC could affect the polarization and activation of macrophages under different conditions. The results show that infusion of GMSC to AopE-/- mice significantly reduced the frequency of inflammatory monocytes/macrophages and decreased the plaque size and lipid deposition. Additionally, GMSC treatment markedly inhibited macrophage foam cell formation and reduced inflammatory macrophage activation, converting inflammatory macrophages to anti-inflammatory macrophages in vitro. Thus, our study has revealed a significant role of GMSC on modulating inflammatory monocytes/macrophages and alleviating atherosclerosis.
| S-EPMC5937358 | biostudies-literature
Project description:Presently, bone marrow is considered as a prime source of mesenchymal stem cells; however, there are some drawbacks and limitations. Compared with other mesenchymal stem cell (MSC) sources, gingiva-derived mesenchymal stem cells (GMSCs) are abundant and easy to obtain through minimally invasive cell isolation techniques. In this study, MSCs derived from gingiva and bone marrow were isolated and cultured from mice. GMSCs were characterized by osteogenic, adipogenic and chondrogenic differentiation, and flow cytometry. Compared with bone marrow MSCs (BMSCs), the proliferation capacity was judged by CCK-8 proliferation assay. Osteogenic differentiation was assessed by ALP staining, ALP assay and Alizarin red staining. RT-qPCR was performed for ALP, OCN, OSX and Runx2. The results indicated that GMSCs showed higher proliferative capacity than BMSCs. GMSCs turned more positive for ALP and formed a more number of mineralized nodules than BMSCs after osteogenic induction. RT-qPCR revealed that the expression of ALP, OCN, OSX and Runx2 was significantly increased in the GMSCs compared with that in BMSCs. Moreover, it was found that the number of CD90-positive cells in GMSCs elevated more than that of BMSCs during osteogenic induction. Taking these results together, it was indicated that GMSCs might be a promising source in the future bone tissue engineering.
| S-EPMC6815943 | biostudies-literature
Project description:The generation of induced-pluripotential stem cells- (iPSCs-) derived mesenchymal stem cells (iMSCs) is an attractive and promising approach for preparing large, uniform batches of applicable MSCs that can serve as an alternative cell source of primary MSCs. Appropriate culture surfaces may influence their growth and differentiation potentials during iMSC derivation. The present study compared molecular properties and differentiation potential of derived mouse iPS-MSCs by deriving on gelatin or collagen-coated surfaces. The cells were derived by a one-step method and expressed CD73 and CD90, but CD105 was downregulated in iMSCs cultured only on gelatin-coated plates with increasing numbers of passages. A pairwise scatter analysis revealed similar expression of MSC-specific genes in iMSCs derived on gelatin and on collagen surfaces as well as in primary mouse bone marrow MSCs. Deriving iMSCs on gelatin and collagen dictated their osteogenic and adipose differentiation potentials, respectively. Derived iMSCs on gelatin upregulated Bmp2 and Lif prior to induction of osteogenic or adipose differentiation, while PPAR? was upregulated by deriving on collagen. Our results suggest that extracellular matrix components such as gelatin biases generated iMSC differentiation potential towards adipose or bone tissue in their derivation process via up- or downregulation of these master genes.
| S-EPMC5014975 | biostudies-literature
Project description:Olfactory ecto-mesenchymal stem cells (OE-MSCs) are a population of cells which has been recognized as a new resident stem cell type in the olfactory lamina propria. OE-MSCs have been shown to exert their immunosuppressive capacity by modulating T cell responses, including up-regulation of regulatory T cells (Tregs) and down-regulation of Th1/Th17 cells. As an inflammatory cytokine, IL-17 plays a critical role in orchestrating the inflammatory response during the development of collagen-induced arthritis (CIA). However, it is unclear whether the increased level of IL-17 may affect the immunosuppressive function of OE-MSCs under inflammatory condition. In this study, we found that IL-17 could significantly reduce the suppressive capacity of OE-MSCs on CD4+ T cells and down-regulate the suppressive factors produced by OE-MSCs. Notably, IL-17 treatment abolished the capacity of OE-MSCs in inducing Treg expansion. In addition, knockdown of IL-17R in OE-MSCs significantly enhanced their therapeutic effect in ameliorating CIA upon adoptive transfer. Moreover, IL-17R knockdown-OE-MSCs could efficiently induce Tregs expansion and reduce Th1 and Th17 responses. Taken together, all these data suggest that IL-17R knockdown in OE-MSCs may provide a novel strategy in maintaining their immunosuppressive properties for the treatment of autoimmune diseases.
| S-EPMC5189999 | biostudies-literature
Project description:Mesenchymal stem cells (MSCs) have multiple properties including anti-inflammatory and immunomodulatory effects in various disease models and clinical treatments. These beneficial effects, however, are sometimes inconsistent and unpredictable. For wider and proper application, scientists sought to improve MSC functions by engineering. We aimed to invent a novel method to produce synthetic biological drugs from engineered MSCs. We investigated the anti-arthritic effect of engineered MSCs in a collagen-induced arthritis (CIA) model. Biologics such as etanercept are the most successful drugs used in anti-cytokine therapy. Biologics are made of protein components, and thus can be theoretically produced from cells including MSCs. MSCs were transfected with recombinant minicircles encoding etanercept (trade name, Enbrel), which is a tumour necrosis factor ? blocker currently used to treat rheumatoid arthritis. We confirmed minicircle expression in MSCs in vitro based on GFP. Etanercept production was verified from the conditioned media. We confirmed that self-reproduced etanercept was biologically active in vitro. Arthritis subsided more efficiently in CIA mice injected with mcTNFR2MSCs than in those injected with conventional MSCs or etanercept only. Although this novel strategy is in a very early conceptual stage, it seems to represent a potential alternative method for the delivery of biologics and engineering MSCs.
| S-EPMC5234034 | biostudies-literature
Project description:Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a clinical condition that specifically occurs in the oral cavity, characterized by retarded wound healing in oral mucosa accelerating the exposure of bone. Moreover, the pathological mechanism remains poorly understood. Gingival mesenchymal stem cells (GMSCs) play a critical role in gingival healing and soft tissue regeneration. Although previous studies have showed that bisphosphonates (BPs) are highly toxic to healthy GMSC, there is overall lack of direct evidence demonstrating the characterization of GMSCs derived from BRONJ patients. In present study, we isolated GMSCs for the first time from the central area of BRONJ patients' gingiva (center-BRONJ GMSCs) and the peripheral area (peri-BRONJ GMSCs), and found that they exhibited decreased proliferation, adhesion, migration capacities and underwent early apoptosis in vitro compared control GMSCs. Notably, the central and peripheral BRONJ GMSCs transplantation in a mice excisional skin model also displayed lower cell survival rate and poor healing effects than that of controls. Mechanistically, TGF-β1 signaling pathway was suppressed not only in BRONJ patients' gingival lesions but also in BRONJ GMSCs transplantation animal model. The results above suggested that under the microenvironment of BRONJ patients, the dysfunction of GMSCs and the suppressed TGF-β1 signaling pathway may be the vital factors in impaired gingival healing, thus contributing to persistent exposure of underlying bone and development of BRONJ. This study provides new insights into the prevention for BRONJ by improving the functions of GMSCs and upregulating TGF-β1 in accelerating gingival wound healing. Schematic illustration of the dysfunction of BRONJ GMSCs in vitro and BRONJ GMSCs transplantation in a mice skin model delaying cutaneous wound healing mainly via suppressing TGF-β1 signaling pathway.
| S-EPMC8799576 | biostudies-literature
Project description:BackgroundAdipose-derived stem cells (ASCs) are mesenchymal stem cells (MSCs) derived from adipose tissue. MSCs have multiple properties including anti-inflammatory and immunomodulatory effects in various disease models and human diseases. However, the mechanisms underlying this wide range of effects need to be explored.MethodsCollagen antibody-induced arthritis (CAIA) is a unique model in which arthritis is rapidly and strongly induced. ASCs were intraperitoneally infused into CAIA mice before or after arthritis induction. The serum levels of various cytokines, adipokines, and chemokines were measured. The expression of FC gamma receptors (FCGRs) was investigated in peritoneal macrophages ex vivo. RAW264.7 cells and ASCs were co-cultured to elucidate the direct and indirect role of ASCs on FCGR expression.ResultsASCs attenuated arthritis in CAIA mice. Serum levels of tumor necrosis factor α, interleukin (IL)-15, resistin, and leptin were reduced in ASC-treated CAIA mice, whereas serum levels of IL-6 and adiponectin were not affected. In peritoneal macrophages isolated from ASC-treated mice, expression of FCGRIIB, which is immunoinhibitory, was higher than that of FCGRI. Co-culture of ASCs with RAW264.7 cells modulated the expression of FCGRs. The expression patterns and timings of peak expression differed among FCGRs. Expression of FCGRIIB was higher and peaked earlier than that of FCGRI. FCGRIII expression was not affected by this co-culture.ConclusionsThis is a study to show that ASCs have anti-arthritic effects in CAIA mice. Modulation of FCGRs by ASCs might be a therapeutic mechanism in this antibody-associated arthritis model.
| S-EPMC4515315 | biostudies-literature