Modulation of mirna155 and mirna133 by bone marrow mesenchymal stem cells in a rat model of asthma: intratracheal versus intravenous administration

Mahdi Ahmadi,1,*

1. Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences



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. the overall goal of current study was to compare the effects of msc after either local or systemic administration on the modulation of mirna155 and mirna133 in ova-inducted asthmatic male rats.


36 male rats, weighing between 200-250 g, were enrolled to the current study. 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 intravenously 2 × 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 ± 1 days. 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 were evaluated.


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 mirna155 were 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.


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.


Asthma, msc, intravenously, intratracheally