GSE211620
The effects of adipose tissue-derived mesenchymal stem cells intranasal administration on the house dust mite-induced mixed airway inflammation in an experimental asthma model
The beneficial effects of mesenchymal stem cell administration have been reported in numerous preclinical studies. Briefly, decreased levels of Th2-related cytokines, namely IL-4, IL-5, and IL-13, impaired eosinophils infiltration, and mucus secretion within the lung have been recognized as hallmarks of MSC-mediated immunosuppression in OVA-Alumn- induced experimental model. However, to date, the effects of MSCs transfer on mixed airway inflammation remain elusive. Therefore, here we aimed to investigate the influence of internasal adipose tissue-derived MSCs on mixed inflammation in a house dust mite (HDM) extract-induced experimental asthma model.  To induce mixed airway inflammation, mice were challenged with 10 ?g of HDM extract for 5 days each week. Additionally, to investigate the short- and long-term effects, adipose tissue-derived MSCs were administrated at two-time points. To analyze MSC-mediated changes, we assessed lung morphology, frequencies of T cells effectors, epithelial barrier integrity, lung transcriptomic profiles, and the levels of cytokines and chemokine in bronchoalveolar lavage (BAL). We observed the limitation of cellular infiltration and mucus production after MSCs administration. Moreover, we noted a trend to decrease in the frequencies of T cells producing IL-4 and IFNy as a long-term effect of MSCs administration. Additionally, the expression of ZO-1 was increased in both analyzed time-points of MSCs transfer. Notably, we found the changes in the transcriptomic profiles reflecting, the inflammation of the respiratory system, the proliferation of lymphocytes, migration of leukocytes, and recruitment of neutrophils and eosinophils. Finally, we also noted the differences in the levels of CXCL and CCL chemokines in BAL between short- and long-term models, while the changes in Th2-related cytokines levels were limited. Overall, here we confirmed the therapeutic potential of adipose tissue-derived MSCs administration in a novel HDM extract-induced experimental model of mixed airway inflammation. Overall design: Female C57BL6 mice (n=5) were challenged intranasally with house dust mite (HDM) extract in the dose of 10ug for 5 following days each of two weeks. Adipose tissue-derived MSCs (5*105 cells) were administrated to mice intranasally on the 13th and 6th day of the experiment to investigate their short- and long-term effects, respectively. Saline (0,9% NaCl) treated mice were set as control. Mice were sacrificed on the 15th day. Lung lobes were collected for histology, flow cytometry, confocal microscopy, and RNA-seq analysis, while bronchoalveolar lavage (BAL) was preserved for multiplex assay.