Effect of bone marrow derived mesenchymal stem cells on lung pathology and inflammation in ovalbumin-induced asthma in mouse (original) (raw)
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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.
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...
Mesenchymal stem cells ameliorate the histopathological changes in a murine model of chronic asthma
International Immunopharmacology, 2011
Asthma therapies are effective in reducing inflammation but airway remodeling is poorly responsive to these agents. New therapeutic options that have fewer side effects and reverse chronic changes in the lungs are essential. Mesenchymal stem cells (MSCs) are promising for the development of novel therapies in regenerative medicine. This study aimed to examine the efficacy of MSCs on lung histopathology in a murine model of chronic asthma. BALB/c mice were divided into four groups: Group 1 (control group, n = 6), Group 2 (ovalbumin induced asthma only, n = 10), Group 3 (ovalbumin induced asthma + MSCs, n = 10), and Group 4 (MSCs only, n = 10). Histological findings (basement membrane, epithelium, subepithelial smooth muscle thickness, numbers of goblet and mast cells) of the airways and MSC migration were evaluated by light, electron, and confocal microscopes. In Group 3, all early histopathological changes except epithelial thickness and all of the chronic changes were significantly ameliorated when compared with Group 2. Evaluation with confocal microscopy showed that no noteworthy amount of MSCs were present in the lung tissues of Group 4 while significant amount of MSCs was detected in Group 3. Serum NO levels in Group 3, were significantly lower than Group 2. The results of this study revealed that MSCs migrated to lung tissue and ameliorated bronchial asthma in murine model. Further studies are needed to evaluate the efficacy of MSCs for the treatment of asthma.
Iranian journal of allergy, asthma, and immunology, 2017
Bone marrow-derived mesenchymal stem cells (BMSCs) can ameliorate a variety of lung diseases such as asthma, lung fibrosis, and acute lung injury by its anti-inflammatory and immunmodulatory effects. In this study, we developed a mouse model of bronchiolitis obliterans (BO) and evaluated the effects of the intraperitoneal administration of BMSCs on lung histopathology and cytokine levels. 25 BALB/c mice were divided into four groups; control group (Group I), BO developed and 1x106 BMSCs-injected group (Group II), non-BO, 1x106 BMSCs-injected group (Group III), and BO developed and saline-injected group (Group IV). Histological and immunohistochemical findings of the lung tissue and the migration of BMSCs to the lung were evaluated using light and confocal microscopy techniques. Confocal microscopy evaluations showed that there was no noteworthy amount of BMSCs in the lung tissue of group III while significant amount of BMSCs was detected in group II. Wall thicknesses of terminal bro...
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.
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...
Stem Cells, 2016
Mesenchymal stem cell (MSC) immunosuppressive functions make them attractive candidates for anti-inflammatory therapy in allergic asthma. However, the mechanisms by which they ensure therapeutic effects remain to be elucidated. In an acute mouse model of house dust mite (Der f)-induced asthma, one i.v. MSC injection was sufficient to normalize and stabilize lung function in Der f-sensitized mice as compared to control mice. MSC injection decreased in vivo airway responsiveness and decreased ex vivo carbachol-induced bronchial contraction, maintaining bronchial expression of the inhibitory type 2 muscarinic receptor. To evaluate in vivo MSC survival, MSCs were labeled with PKH26 fluorescent marker prior to i.v. injection, and 1 to 10 days later total lungs were digested to obtain single-cell suspensions. 91.5 ± 2.3% and 86.6 ± 6.3% of the recovered PKH26+ lung cells expressed specific macrophage markers in control and Der f mice, respectively, suggesting that macrophages had phagocyt...
Mesenchymal stem cell (MSC) immunosuppressive functions make them attractive candidates for anti-inflammatory therapy in allergic asthma. However, the mechanisms by which they ensure therapeutic effects remain to be elucidated. In an acute mouse model of house dust mite (Der f)-induced asthma, one i.v. MSC injection was sufficient to normalize and stabilize lung function in Der f-sensitized mice as compared to control mice. MSC injection decreased in vivo airway responsiveness and decreased ex vivo carbachol-induced bronchial contraction, maintaining bronchial expression of the inhibitory type 2 muscarinic receptor. To evaluate in vivo MSC survival, MSCs were labeled with PKH26 fluorescent marker prior to i.v. injection, and 1 to 10 days later total lungs were digested to obtain single-cell suspensions. 91.5 6 2.3% and 86.6 6 6.3% of the recovered PKH26 1 lung cells expressed specific macrophage markers in control and Der f mice, respectively, suggesting that macrophages had phagocyted in vivo the injected MSCs. Interestingly, only PKH26 1 macrophages expressed M2 phenotype, while the innate PKH26 2 macrophages expressed M1 phenotype. Finally, the remaining 0.5% PKH26 1 MSCs expressed 10-to 100-fold more COX-2 than before injection, suggesting in vivo MSC phenotype modification. Together, the results of this study indicate that MSCs attenuate asthma by being phagocyted by lung macrophages, which in turn acquire a M2 suppressive phenotype.
Unraveling the therapeutic effects of mesenchymal stem cells in asthma
Stem Cell Research & Therapy, 2020
Asthma is a chronic inflammatory disease associated with airway hyper-responsiveness, chronic inflammatory response, and excessive structural remodeling. The current therapeutic strategies in asthmatic patients are based on controlling the activity of type 2 T helper lymphocytes in the pulmonary tissue. However, most of the available therapies are symptomatic and expensive and with diverse side outcomes in which the interruption of these modalities contributes to the relapse of asthmatic symptoms. Up to date, different reports highlighted the advantages and beneficial outcomes regarding the transplantation of different stem cell sources, and relevant products from for the diseases’ alleviation and restoration of injured sites. However, efforts to better understand by which these cells elicit therapeutic effects are already underway. The precise understanding of these mechanisms will help us to translate stem cells into the clinical setting. In this review article, we described curre...