Therapeutic potential of human stem cell-derived extracellular vesicles in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a lethal and chronic lung disease that occurs due to persistent epithelial cell injury and abnormal extracellular matrix (ECM) deposition. Extracellular vesicles (EVs) have been proposed as a potential therapeutic option of IPF because of their functions, such as anti-inflammation, anti-fibrosis, microenvironment regulation, and tissue repair. In this study, we investigated the therapeutic potential of human adipose-derived mesenchymal stem cell (AD-MSC) EVs in IPF model. AD-MSC EVs were isolated by a multi-filtration system based on the tangential flow filtration (TFF) and characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), flow cytometry analysis, zeta potential, and small RNA sequencing. In vitro analysis reveals that AD-MSC EVs treatments inhibited migration of pulmonary fibroblasts and myofibroblast differentiation through down regulation of fibrosis-associated TGF-β and WNT signaling. In addition, inhalation treatment of AD-MSC EVs significantly alleviated bleomycin (BLM)-induced pulmonary fibrosis. These results reveal that AD-MSC EVs are highly promising as a treatment option for pulmonary fibrosis.