Pulmonary fibrosis (PF) is a severe chronic
lung disease with little effective treatment options other than
lung transplantation. Adipose-derived mesenchymal stem cells (ADSCs) have been shown to exert
therapeutic effects on PF, but the underlying mechanisms remain to be further elucidated. Here, we show the interaction of ADSCs and lung-originated cells at the single-cell level, using
bleomycin- (BLM-) induced mice PF model and
green fluorescent protein- (GFP-) labeled mouse ADSCs. The intratracheally injected ADSCs were successfully recollected with flow cytometry and, together with lung-originated cells, were subjected to single-cell
RNA sequencing (
scRNA-seq). The ADSC treatment drastically changed the transcriptomic profile and composition of lung cells, especially macrophages. We explored the signal pathway interactions between ADSCs and lung-originated cells, showing potentially regulative pathways including NGR,
ANNEXIN, HGF, and
PERIOSTIN. Our data indicate that the injected ADSCs increased the number of Trem2 + antiinflammatory lung macrophages and lowered further
inflammation and
fibrosis in the lung. Our work realized the direct analysis of injected ADSCs to explore its in vivo interaction with the lung environment under PF and may provide critical information for future engineering of ADSCs to achieve better
therapeutic effects in PF.