Mesenchymal stem cells ameliorate the histopathological changes in a murine model of chronic asthma

Abstract

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.

Mesenchymal Stromal Cells Mediate Aspergillus Hyphal Extract-Induced Allergic Airway Inflammation by Inhibition of the Th17 Signaling Pathway

“…We and others have found that in mouse models of mild Th2-eosinophilic mediated AAI, systemic administration of MSCs either during initial sensitization or during challenge significantly ameliorates both AHR and lung inflammation [27][28][29][30][31][32][33][34][35][36][37][38]. In the current study, we demonstrated that systemic MSC administration during challenge ameliorates AHR and lung inflammation in a more severe model of acute mixed Th2/Th17-mediated neutrophilic AAI induced by mucosal exposure to and challenge with adjuvant-free AHE.…”

“…Limited available data suggest that MSCs or MSCconditioned media can have effects in models of chronic AAI, but the mechanisms are unclear [27][28][29][30][31][32]. In the current studies, MSC administration during a recurrent challenge decreased AHR but not lung inflammation and paradoxically stimulated a significant increase in BAL fluid neutrophils.…”

“…With respect to asthma, MSCs have been demonstrated to ameliorate experimentally induced T helper cell (Th) type 2-mediated eosinophilic allergic airway inflammation (AAI) in mice [27][28][29][30][31][32][33][34][35][36][37][38]. Immunogens investigated in models include sensitization and challenge with ovalbumin, ragweed pollen, dust mite antigen, and toluene diisocyanate, and comparable effects have been observed with syngeneic, allogeneic, or xenogeneic MSC administration.…”

Mesenchymal Stem Cells: A Promising Therapy for the Acute Respiratory Distress Syndrome

“…Several studies have demonstrated the potential therapeutic effect of MSCs in different diseases: myocardial infarction [41,42,43,44], pulmonary fibrosis [45,46], pulmonary hypertension [47,48,49,50], emphysema [51,52,53], diabetes [54], sepsis [55,56], asthma [57], hepatic failure [58], acute renal failure [59] and ARDS [5,38,60,61,62,63,64]. In all preclinical studies, infused MSCs expanded in vitro were used.…”

The Implications of Stem Cell Applications for Diseases of the Respiratory System

“…Sun and colleagues (2011) demonstrated that the intravenous administration of autologous adipose-derived MSCs could attenuate the inflammatory response and oxidative stress in an acute rat ischemia-reperfusion lung injury model [12]. In experiments using asthma as a model for chronic lung disease, it was shown that the decline in lung function was inhibited by rat bone marrow MSCs [13,14]. This was achieved by reducing airway hyperactivity, inflammation, and remodeling.…”