Comprehensive analysis of the lung

Comprehensive analysis of the lung transcriptome revealed ASCs induce a substantial transcriptomic response in the absence of infection, which was associated with various tissue stress and damage pathways, for example, elevated protein ubiquitination pathway genes, granulocyte adhesion and diapedesis genes, unfolded protein response genes, fibrosis, and acute phase response signaling. In the context of lung infection, ASC treatment further increased tissue stress responses, concomitant with a substantial decrease in innate and adaptive immune responses. The reduction in expression of genes involved in innate and adaptive immune responses is in line with the hypothesis that MSCs, in general, may inhibit the exaggerated host immune response that eventually results in organ damage [11, 62]. In addition, we showed that T helper cell activation and granulocyte adhesion and diapedesis pathways were particularly affected by ASCs treatment of K. pneumoniae lung infection. With reference to enhanced expression of genes implicated in fibrotic responses in animals infused with ASCs, it should be noted that the current model is acute and fibrosis cannot be detected at histological level. In more chronic settings, infusion of MSCs have been shown to exert antifibrotic effects in the lungs in several experimental settings, including lung fibrosis induced by bleomycin [63, 64], white smoke [65], silica [66], and chronic allergic airway inflammation [67]. These preclinical data led several investigators to suggest infusion of MSCs as a potential novel therapeutic for lung fibrosis in patients [68, 69]. Nonetheless, although the acute effect of ASCs on expression of genes involved in fibrosis is less likely to cause fibrosis in the long-term, this has to be monitored in clinical trials with patients suffering from pneumonia.