Single-cell RNA Sequencing Reveals That Injected ADSCs Change the Macrophage Profile in a Murine Model of Pulmonary Fibrosis

Abstract Background: Idiopathic pulmonary fibrosis (IPF) is a deadly chronic interstitial lung disease with no effective treatment options other than lung transplantation. Allogeneic adipose-derived mesenchymal stem cells (ADSCs) are considered ideal as seed cells for stem cell-based therapy, and some studies illustrated the therapeutic effect of ADSCs on IPF, but the underlying mechanisms remain unclear.Methods: A single intratracheal dose of bleomycin (BLM) was administered to induce pulmonary injury/fibrosis in C57BL/6 mice, after GFP-labeled mouse ADSCs (mADSCs) were implanted intratracheally to explore their potential therapeutic effects in the inflamed/fibrotic lung microenvironment. The mADSCs were then retrieved through fluorescence-activated cell sorting and subjected to single-cell RNA sequencing (scRNA-seq).Results: Our data indicate that the single-dose intratracheal administration of mADSCs could significantly increase the life span of IPF mice by remodeling the extracellular matrix and promoting the polarization of macrophages to an anti-inflammatory phenotype. Conclusions: A single intratracheal injection of mADSCs alleviated BLM-induced pulmonary fibrosis by readjustment of the mouse lung microenvironment, which was reflected in changes of the lung C1QB+, APOE+ and TREM2+ macrophages in the mouse model.