| خلاصه مقاله | Abstract
Introduction: Asthma is commonly regarded as a debilitating chronic respiratory disorder caused by a plethora of factors with profound impacts on socioeconomic costs. Based on statis¬tics, asthma involves approximately 300 million people of all ages worldwide without any definite therapeutic approach. Histopathological changes in the lung tissues of asthmatic subjects are mainly induced by the chronic inflammatory responses due to the up-regulation of cytokines produced by type 2 T helper cells (Th2) .Therefore, new therapeutic manipulations for asthma must be considered, not only to manage asthma-related manifestations, but also to accelerate the regeneration rate of chronic structural changes focusing on the reversal of Th2/Th1 imbalance and the control of inflammation rate in the lung airway structures. Owning immune-modulatory features, it makes MSCs eligible to be used broadly for ameliorating chronic lung diseases such as asthma. Due to specific anatomical and histological characteristics, lungs are good candidate for MSCs administration, certainly either by local or systemic routes. MicroRNAs (miRNAs) are conceived as a novel class of biomarkers for numerous inflammatory diseases. miRNAs were found to participate in airway inflammatory regulation via the modulation of Th2 cell function . In close relation to this statement, it has been shown that numerous miRNAs expressed differently in lung tissue of OVA-challenged mice.The overall goal of current study was to compare the effects of MSC after either local or systemic administration on the modulation of miRNA155and miRNA133in OVA-inducted asthmatic male rats.
Materials and methods: In this study, 36 healthy mature male Wistar rats with body weight at range of 200–250 g were used. The animals were accommodated in standard cages at 20 ± 2°C under 12:12 light/dark cycle with free access to food and water. Four healthy rats were randomly used for extraction of rat bone marrow-derived MSCs (rBMMSCs). The remaining 32 animals were assigned into four experimental groups (n =8 per group); control rats (C group), asthmatic rats (A group), asthmatic rats received intravenously2 × 106 MSCs (ACV group) and asthmatic rats received intratracheally 2 × 106 MSCs(ACT group).In ovalbumin (OVA)-sensitized groups, rats were exposed to OVA for a period of 32 ± 1days.In control group, rats received saline instead of OVA. Two weeks post treatment with stem cells (day 48); the expression levels of miRNA133 and miRNA155 as well as histopathological changes including vascular changes, hyperemia and respiratory epithelial hyperplasia were evaluated.
Results: Our pathological results revealed that lesions observed in the lung tissue of asthmatic groups were significantly higher than the control rats (p<0.001 to p<0.05), confirming the rat model of asthma was constructed efficaciously. In addition, a significant reduction in the expression of miRNA133 coin¬cided with a remarkable increase in the expression of miRNA155were seen in all sensitized groups as compared with healthy rats. The systemic and direct injection of MSCs, decreased pathological injures in OVA-sensitized rats by the modulation of expression levels of miRNA133 and miRNA155 in lung tissues of OVA-sensitized rats (p<0.001 to p<0.05), although these changes were more evident in local route ((Figs a, b).
Conclusion: Our objective of selecting an appropriate cell fraction was to demonstrate the paracrine therapeutic effect of MSCs after either intratracheal or intravenous administration separately on ameliorating OVA-inducted asthmatic changes with focus on the lung inflammation and to compare the potential therapeutic effects of the two interventions. The elucidation of the underlying mechanisms governed by MSCs in asthma will help to achieve the beneficial clinical application for stem cell therapy in human medicine. There¬fore, we here hypothesized that MSC-mediated immune-modulatory properties would be directed via the regulation of miRNA expression in asthmatic lung tissue The results of this study showed systemic and direct injection of MSCs could be effective in alleviation of asthma pathophysiology, possibly via the modulation of miRNA133 and miRNA155. However, the regenerative responses observed post local administrations of MSCs were higher than systemic route. |