Mesenchymal stem cell administration changes transcriptomic profiles of non-inflamed lungs in mice.

Here, we report that intranasal administration of MSCs to non-inflamed lung microenvironment changed transcriptomic profiles compared to control group. We found 674 differentially regulated genes unique for the short-term model, while only 75 genes were unique for the prolonged observations, suggesting waning of the low-grade inflammation and active resolution in the longer time point. Moreover, we evaluated the enrichment of differentially expressed genes (DEGs) in the gene ontologies, signaling pathways, and mapped predicted interactions using clusterProfiler v.4.0.0. The normalized enrichment score (NES) analysis indicated activation of the innate and adaptive immune responses. More precisely, the analysis of activation canonical pathways in Ingenuity Pathway Analysis (IPA) software revealed the increase in IL-7 signaling, T and B cell signaling in the short- and long-term models compared to controls. In addition to this observation, we noted gradual downregulation in HIF1a signaling, IL-17 signaling, and B cell receptor signaling in the longer time-point. Furthermore, the analysis of expression of genes clustered to the terms and processes related to airway inflammation, namely Th1-, Th2-, Th17- driven immune responses development, tight junction molecules, and mucins, revealed a relatively low number of significantly changed genes. Next, we analyzed deeper the expression profiles of genes related to oxidative stress and immune responses, focusing on macrophages activation and phagocytosis. We noted the dysregulated expression of pattern recognition receptors (PRRs) macrophage activation, oxidative stress, phagocytosis, and inflammation of the respiratory system. Furthermore, we analyzed the most significant genes with altered z-scores at the investigated time-points according to the Ingenuity Pathway Analysis. We observed a trend in a longitudinal decrease in the expression of the shared genes. This study provides a new knowledge regarding a changes in lung transcriptomic profiles in mice administrated with adipose tissue- derived MSCs. Overall design: Female 6-8-week-old C57BL/6 mice were divided into three groups. Mice were sacrificed after 2 (short-term) and 9 (long-term) days from adipose-tissue-derived MSCs administration intranasally. Biological material was collected and biobanked for further analysis.