[Show abstract][Hide abstract] ABSTRACT: Although several studies have demonstrated that mesenchymal stem cells derived from adipose tissue (ASCs) can ameliorate allergic airway inflammation, the immunomodulatory mechanism of ASCs remains unclear. In this study, we investigated whether regulatory T cells (Tregs) induction is a potential mechanism in immunomodulatory effects of ASCs on allergic airway disease and how these induced Tregs orchestrate allergic inflammation. Intravenous administration of ASCs significantly reduced allergic symptoms and inhibited eosinophilic inflammation. Airway hyperresponsiveness, total immune cell and eosinophils in the bronchoalveolar lavage fluid, mucus production, and serum allergen-specific IgE and IgG1 were significantly reduced after ASCs administration. ASCs significantly inhibited Th2 cytokines (IL-4, IL-5, and IL-13) and enhanced Th1 cytokine (IFN-γ) and regulatory cytokines (IL-10 and TGF-β) in the bronchoalveolar lavage fluid and lung draining lymph nodes. Furthermore, levels of IDO, TGF-β, and PGE2 were significantly increased after ASCs administration. Interestingly, this upregulation was accompanied by increased Treg populations. In conclusion, ASCs ameliorated allergic airway inflammation and improved lung function through the induction of Treg expansion. The induction of Treg by ASCs involves the secretion of soluble factors such as IDO, TGF-β, and PGE2 and Treg might be involved in the downregulation of Th2 cytokines and upregulation of Th1 cytokines production.
Full-text · Article · Aug 2014 · Mediators of Inflammation
[Show abstract][Hide abstract] ABSTRACT: Adipose tissue-derived stem cells (ASCs) have been reported to have immunomodulatory effects in various inflammatory diseases, including asthma and allergic rhinitis, through the induction of T cell anergy. Nasal polyps (NPs) are a chronic inflammatory disease in the nose and paranasal sinus characterized histologically by the infiltration of inflammatory cells, such as eosinophils or lymphocytes. This study was performed to investigate whether ASCs have immunomodulatory effects on T lymphocyte and cytokine expression in eosinophilic NPs.
Basic science experimental study.
University tertiary care facility.
NP specimens were obtained from 20 patients with chronic rhinosinusitis and eosinophilic NPs. ASCs were isolated and cultured from the abdominal fat of 15 subjects undergoing intra-abdominal surgery. Infiltrating cells (1 × 10(6)) were isolated from NP tissue and co-cultured with 1 × 10(5) ASCs. To determine whether ASCs affect infiltrating T lymphocyte and cytokine expression in eosinophilic NP, T lymphocyte subsets and cytokine expression were analyzed before and after ASC treatment.
ASC treatment significantly decreased the proportions of CD4(+) and CD8(+) T cells. After ASC treatment, Th2 cytokine (interleukin [IL]-4 and IL-5) levels decreased significantly. In contrast, levels of Th1 (interferon-γ and IL-2) and regulatory cytokines (transforming growth factor-β and IL-10) increased significantly after ASC treatment.
ASCs have immunomodulatory effects in the eosinophilic inflammation of NPs, characterized by down-regulation of activated T lymphocytes and a Th2 immune response. These effects would be expected, over time, to significantly contribute to the control of eosinophilic inflammation and, possibly, growth of eosinophilic NPs.
Full-text · Article · Mar 2014 · Otolaryngology Head and Neck Surgery
[Show abstract][Hide abstract] ABSTRACT: The identification of new progenitor cell sources is important for cell-based tissue engineering strategies, understanding regional tissue regeneration, and modulating local microenvironments and immune response. However, there are no reports that describe the identification and isolation of mesenchymal progenitor cells (MPCs) from paranasal sinus mucosa, and compare the properties of MPCs between tissue sources within the sinonasal cavity. We report here the identification of MPCs in the maxillary sinus (MS) and ethmoid sinus (ES). Furthermore, we contrast these MPCs in the same individuals with MPCs from two additional head and neck tissue sources of the inferior turbinate (IT) and tonsil (T).
These four MPC sources were exhaustively compared for morphology, colony-forming potential, proliferation capability, immunophenotype, mulitilineage differentiation potential, and ability to produce soluble factors.
MS-, ES, IT-, and T-MPCs showed similar morphologies and surface phenotypes, as well as adipogenic, osteogenic, and chondrogenic differentiation capacity by immunohistochemistry and qRT-PCR for defined lineage-specific genes. However, we noted that the colony-forming potential and proliferation capability of ES-MPCs were distinctly higher than other MPCs. All MPCs constitutively, or upon stimulation, secrete large amounts of IL-6, IL-8, IL-10, IFN-gamma, and TGF-beta. After stimulation with TNF-alpha and IFN-gamma, ES-MPCs notably demonstrated significantly higher secretion of IL-6 and IL-10 than other MPCs.
ES-MPCs may be a uniquely promising source of MPCs due to their high proliferation ability and superior capacity toward secretion of immunomodulatory cytokines.
Full-text · Article · Jan 2014 · Stem Cell Research & Therapy
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to compare murine mesenchymal stem cells (MSCs) isolated from bone marrow (BM) and adipose tissue (AT) for the selection of suitable MSCs in cell therapy of an airway allergic animal model. We compared MSCs of BALB/c mice derived from BM and AT with respect to proliferation potential, immunophenotype, and multilineage differentiation capacity. In proliferation potential, MSCs from AT (ASCs) showed higher fibroblastoid colony-forming units frequencies and colony-forming efficiency than MSCs from BM (BMSCs). The flow cytometry analysis showed that both ASCs and BMSCs expressed MSCs-related antigens (CD90 and CD105), whereas they did not express hematopoiesis-related antigens (CD45 and CD11b). There was no significant difference in adipogenic, osteogenic, and chondrogenic differentiation between the murine ASCs and BMSCs. In conclusion, the present study has shown that ASCs had higher CFU-F frequencies and colony-forming efficiency than BMSCs. ASCs and BMSCs presented a similar surface immunophenotype and multilineage differentiation capacity. Therefore, ASCs in BALB/c mice might be a more useful material for cell therapy of the airway allergic experiment due to the abundance, relatively easy harvesting and high proliferation potential.
[Show abstract][Hide abstract] ABSTRACT: The major aims of this study were to characterize the varieties of T-cell infiltrates in tissue collected from patients with chronic rhinosinusitis with nasal polyps (CRSwNP), analyze the cytokine profiles of these infiltrating T cells, and determine whether infiltrating T lymphocytes are specific for superantigens (SAGs).
Anterior ethmoid sinus mucosa and polyp tissue were collected from 23 patients with CRSwNP, and control anterior ethmoid sinus mucosa were obtained from 20 patients without CRS. Infiltrating cells were isolated from tissue samples and analyzed using flow cytometry, enzyme-linked immunosorbent assay, reverse transcriptase-polymerase chain reaction, and in vitro T-lymphocyte stimulation with Staphylococcus aureus.
The mean total numbers and proportions of CD3+, CD4+, and CD8+ T cells were significantly higher in the mucosa and polyp tissue of patients with CRSwNP than in the control group. Most infiltrating T cells in patients with CRSwNP were activated CD45RO+ memory T cells. Furthermore, interferon-γ (IFN-γ) expression was significantly higher than interleukin (IL)-10 and IL-4 expression in infiltrating T cells isolated from both the mucosa and the polyp tissue. IFN-γ also showed significantly greater increases in expression compared to IL-4 and IL-10 when isolated T cells were stimulated with SAGs in vitro.
IFN-γ-producing T cells could play an important role in CRSwNP when sinonasal chronic inflammation is induced by SAGs.
Full-text · Article · Oct 2010 · Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale
[Show abstract][Hide abstract] ABSTRACT: Allergic asthma is an inflammatory airway disease caused by T helper type 2 (Th2)-driven immune responses. Recent studies have demonstrated that adipose-derived stromal cells (ASC) have an immunosuppressive effect on T-cell activity. This study was performed to investigate whether ASC can inhibit Th2-dependent allergic airway inflammation in mice. BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injection. To investigate the effect of ASC on the development of asthma phenotypes, 2 × 10⁶ ASC were injected intravenously before OVA challenge. We evaluated the airway hyperresponsiveness (AHR), the proportion of eosinophils and cytokine production in bronchoalveolar lavage fluid (BALF), airway inflammation, and the intracellular cytokine staining of T cells in the BALF and spleen. Airway hyperresponsiveness, airway eosinophilia, and mucus production were markedly reduced after ASC administration before OVA challenge. The increased interleukin (IL)-4, IL-5, and transforming growth factor (TGF)-β1 levels in the BALF after OVA challenge were significantly reduced by the administration of ASC. This inhibition was accompanied by decreased IL-4(+) CD4(+) T cells and increased interferon (IFN)-γ(+) CD4(+) T cells in the BALF and spleen. The results of this study suggest that ASC administration before an allergen challenge inhibits AHR, lung inflammation, and Th2 cytokine production induced by an allergen challenge through inhibition of Th2 cell activity.
Full-text · Article · Mar 2010 · Stem cells and development
[Show abstract][Hide abstract] ABSTRACT: Adipose tissue-derived stem cells (ASCs) exhibit immunosuppressive effects in allogeneic transplantation. However, there is no report that evaluates the in vivo immune-modulating effect of ASCs in an experimental allergic rhinitis (AR) model. We investigated whether ASCs migrate to the nasal mucosa in an AR mouse model and evaluated the immune-modulating effect of ASCs in the AR mouse model. Cultured ASCs (2 x 10(6)) were injected i.v. before the first allergen challenge in the AR mouse model. Migration of ASCs to the nasal mucosa was evaluated by immunofluorescence. The immunomodulatory effects of ASCs were evaluated by nasal symptoms, histology, serum ovalbumin (OVA)-specific antibody, and the cytokine profile of the spleen. ASCs migrated to the nasal mucosa in the AR mouse model. ASCs significantly reduced allergic symptoms and inhibited eosinophilic inflammation in the nasal mucosa. ASCs significantly decreased the serum allergen-specific IgE level and the IgG(1)/IgG(2a) ratio and significantly increased the IgG(2a) level in the AR mouse model. ASCs inhibited interleukin (IL)-4 and IL-5 production from OVA-incubated splenocytes, but enhanced interferon-gamma production. In conclusion, ASCs can migrate to the nasal mucosa in the AR mouse model and inhibit eosinophilic inflammation partly via shifting to a T-helper 1 (Th1) from a Th2 immune response to allergens.