Dental follicle mesenchymal stem cells down‐regulate Th2‐mediated immune response in asthmatic patients mononuclear cells (original) (raw)
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Allergologia et Immunopathologia, 2019
Background: House dust mite (Dermataphagoides pteronyssinus) is a widespread risk factor in the development of asthma. CD4 + T lymphocytes have an important role in the pathogenesis of allergic asthma by polarizing to Th2 cells. Objective: We aimed to evaluate the immunoregulatory effects of dental follicle mesenchymal stem cells with and without IFN-␥ stimulation on peripheral blood mononuclear cells of house dust mite sensitive asthmatic patients, and compared those with Dexamethasone as a systemic steroid. Material and methods: PBMC of asthmatic patients and healthy individuals separately cultured with or without DF-MSCs in the presence and absence of IFN-␥ or Der p1 or Dexamethasone for 72 h. CD4 + T proliferation, cell viability, CD4 + CD25 + FoxP3 + Treg cell frequency and cytokine profiles of PBMC were evaluated via flow cytometry. Results: DF-MSCs suppressed proliferation of CD4 + T lymphocytes (p CDmix < 0.01, p Derp1 < 0.01, p IFN < 0.005) by increasing the number of FoxP3 expressing CD4 + CD25 + T regulatory cells (p CDmix < 0.005, p Derp1 < 0.01, p IFN < 0.001) and suppressed lymphocyte apoptosis (p CDmix < 0.05, p Derp1 < 0.05, p IFN < 0.05), while Dexamethasone increased the apoptosis and decreased Treg cell frequency in asthmatic patients. IFN-␥ stimulation increased the suppressive effect of DF-MSCs and also enhanced the frequency of FoxP3 expressing CD4 + CD25 + T regulatory cells. The cytokine levels were regulated by DF-MSCs by reducing IL-4 cytokine levels (p CDmix < 0.01, p Derp1 < 0.05, p IFN < 0.05) and upregulating IFN-␥ levels (p CDmix < 0.01, p Derp1 < 0.05, p IFN < 0.005) in asthmatic patients.
Asthma immunotherapy and treatment approaches with mesenchymal stem cells
Immunotherapy, 2020
Asthma is a chronic inflammatory disease of the airways where exaggerated T helper 2 immune responses and inflammatory mediators play a role. Current asthma treatment options can effectively suppress symptoms and control the inflammatory process; however, cannot modulate the dysregulated immune response. Allergen-specific immunotherapy is one of the effective treatments capable of disease modification. Injecting allergens under the skin in allergen-specific immunotherapy can reduce asthma and improve the sensitivity of the lungs, however, has a risk of severe reactions. Mesenchymal stem cells have immunoregulatory activity with their soluble mediators and contact dependent manner. In this review, we focus on the current treatment strategies with mesenchymal stem cells in asthma as a new therapeutic tool and compare those with immunotherapy.
The Turkish Journal of Gastroenterology
Background/Aims: Crohn's disease (CD) is a chronic inflammatory condition characterized by various abnormalities that lead to overly aggressive T cell responses. Our in vitro experiments aimed to investigate the potential use of Dental Follicle Mesenchymal Stem Cells (DF-MSCs) to suppress the exaggerated immune response in inflamed and noninflamed tissue of CD. Materials and Methods: Dental follicle tissues were obtained from extracted third molar teeth of three healthy volunteers who had no abscess or inflammatory diseases. In total, 11 patients were included in the experiment who had been diagnosed with CD and did not receive steroid maintenance therapy for more than one month. Mononuclear cells were isolated from inflamed and noninflamed tissues of CD. Isolated cells were stimulated with anti-CD3/anti-CD28 monoclonal antibodies in the presence and absence of DF-MSCs and analyzed for lymphocytes proliferation capacity and viability, T lymphocyte subsets, CD4+IL22BP and CD4+CD25+Foxp3+ regulatory T cell (Treg) frequencies and cytokine levels. Results: A significant downregulation of lymphocyte proliferation and CD4+IL22BP T cell ratio were found in inflamed cultures with DF-MSCs (p<0.005). Additionally, the frequency of Tregs increased with DF-MSCs (p<0.05). Proinflammatory cytokine levels (Tumor Necrosis Factor (TNF)-α and IL-6) were decreased (p<0.05), and IL-10 levels were increased (p<0.05) in the supernatant of inflamed cultures. Conclusion: DF-MSCs reduced the inflammatory immune response, induced Tregs, and downregulated CD4+IL22BP T cell ratio in inflamed samples of CD patients, which may be exploited for significant therapeutic use.
Bone marrow-derived mononuclear cells vs. mesenchymal stromal cells in experimental allergic asthma
Respiratory Physiology & Neurobiology, 2013
We compared the effects of bone marrow-derived mononuclear cells (BMMCs) and mesenchymal stromal cells (MSCs) on airway inflammation and remodeling and lung mechanics in experimental allergic asthma. C57BL/6 mice were sensitized and challenged with ovalbumin (OVA group). A control group received saline using the same protocol. Twenty-four hours after the last challenge, groups were further randomized into subgroups to receive saline, BMMCs (2 × 10 6) or MSCs (1 × 10 5) intratracheally. BMMC and MSC administration decreased cell infiltration, bronchoconstriction index, alveolar collapse, collagen fiber content in the alveolar septa, and interleukin (IL)-4, IL-13, transforming growth factor (TGF)- and vascular endothelial growth factor (VEGF) levels compared to OVA-SAL. Lung function, alveolar collapse, collagen fiber deposition in alveolar septa, and levels of TGF- and VEGF improved more after BMMC than MSC therapy. In conclusion, intratracheal BMMC and MSC administration effectively modulated inflammation and fibrogenesis in an experimental model of asthma, but BMMCs was associated with greater benefit in terms of reducing levels of fibrogenesis-related growth factors.
Biomedicine & Pharmacotherapy, 2017
Background: The major feature of asthma is governed by chronic airway inflammation. This investigation was proposed to achieve the suitable candidate for ameliorating long-term chronic asthmatic changes of respiratory tract. Methods: 36 rats were classified into healthy (C) and ovalbumin (OVA)-sensitized animals (S). To sensitize, the rats were exposed to OVA over a course of 32 AE 1 days. One day after sensitization, equal six different groups were subjected to experimental procedure (n = 6); Rats only received intratracheally 50 ml PBS (CPT and SPT groups), 50 ml conditioned medium (CM) (CST and SST groups) and 50 ml PBS containing 2 Â 10 6 rat bone marrow-derived mesenchymal stem cells (rBMMSCs) (CCT and SCT groups). Two weeks after treatment, tracheal responsiveness, immunologic responses and recruitment of rBMMSCs into the lung as well as pathological changes were evaluated. Results: A high degree of tracheal responsiveness, total white blood cell and percentages of eosinophil and neutrophil was significantly recorded in all sensitized groups rather than of controls (p < 0.001 to p < 0.05). Of interest, all above-mentioned parameters decreased significantly in SST and notably SCT groups as compared to S group (p < 0.001 to p < 0.05). The results revealed decrease number of blood CD3 + CD4 + and concurrent increase in CD3 + CD8 + in all sensitized rats as compared to control (p < 0.001 to p < 0.05). Noticeably, no significant modulatory effects of either cell or CM administration were achieved on the CD3 + CD4 + and CD3 + CD8 + populations in non-asthmatic rats. Moreover, the number of CD3 + CD4 + in SST and SCT groups tended to increase, which coincided with a decreased manner of CD3 + CD8 + populations as compared with S group (p < 0.001 to p < 0.05). However, the CD3 + CD4 + cells in SCT rats were significantly higher than the group SST (p < 0.01) whereas CD3 + CD8 + cells diminished simultaneously (p < 0.001). Real-time PCR analysis further showed that both CM and particularly MSCs changed the expression of interleukin (IL)-4 and IL-10 in the asthmatic groups to the near level of control rats (p<0.001 to p < 0.05). Histopathological analysis revealed a profound reduction of lungs injuries in asthmatic rats when received CM and peculiarly mesenchymal stem cells (p < 0.01 to p < 0.05). Conclusion: Our study shed light on the superior effects of rBMMSCs, rather than CM, in attenuating of chronic asthmatic changes in the rat model.
American journal of rhinology & allergy, 2015
Although several studies have claimed that mesenchymal stem cells (MSC) derived from human tissues can ameliorate allergic airway inflammation, the immunomodulatory mechanism of MSCs remains unclear. We aimed to determine the effects and the underlying mechanism of tonsil-derived MSCs (T-MSC) on allergic inflammation compared with adipose tissue-derived stem cells (ASC) in a mouse model of allergic rhinitis (AR). MSCs were isolated from human palatine tonsil (T-MSC) and the surface markers were analyzed. The effect of T-MSCs was evaluated in 24 BALB/c mice that were randomly divided into four groups (negative control group, positive control group, T-MSC group, and ASC group). MSCs were administered intravenously to ovalbumin (OVA) sensitized mice (T-MSC and ASC groups) on days 18 to 23, and subsequent OVA challenge was conducted daily from days 24 to 28. Several parameters of allergic inflammation were assessed. T-MSC and ASC had similar characteristics in surface markers. Intraveno...
2020
Background: Recent attempts to develop more efficacious treatments for asthma, a TH2-dominant disease, have incorporated mesenchymal stem cell (MSC)-based cell therapies. Despite numerous previous studies, the full action mechanism of the pathogenesis of asthma remains undiscovered, and the need for further investigation is increasing in order to identify more effective target molecules. Objective: This study aimed to evaluate the anti-asthmatic effects of intratracheally administered MSCs primed with Liproxstatin-1, a potent ferroptosis inhibitor. In addition, we sought to examine the changes within macrophage populations and their characteristics in asthmatic conditions to explain the pathogenesis of asthma. Methods: Seven-week-old transgenic (TG) mice, constitutively overexpressing lung-specific interleukin (IL)-13, were used to simulate chronic asthma. Human umbilical cord-derived MSCs (hUC-MSCs) primed with Liproxstatin-1 were intratracheally administered four days prior to sam...
AJP: Lung Cellular and Molecular Physiology, 2010
Allogeneic human mesenchymal stem cells (hMSCs) introduced intravenously can have profound anti-inflammatory activity resulting in suppression of graft vs. host disease as well as regenerative events in the case of stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of these diseases. hMSCs produce bioactive factors that provide molecular cuing for: 1) immunosuppression of T cells; 2) antiscarring; 3) angiogenesis; 4) antiapoptosis; and 5) regeneration (i.e., mitotic for host-derived progenitor cells). Studies have shown that hMSCs have profound effects on the immune system and are well-tolerated and therapeutically active in immunocompetent rodent models of multiple sclerosis and stroke. Furthermore, intravenous administration of MSCs results in pulmonary localization. Asthma is a major debilitating pulmonary disease that impacts in excess of 150 million people in the world with uncontrolled asthm...