Extracellular vesicles from adipose-derived mesenchymal stem cells promote stemness and EMT of corneal epithelial stem cells

Corneal diseases are a leading contributor of vision impairment and their treatment remains challenging. It’s known that enhancement of the stemness of corneal epithelial stem cells (CECs) plays a pivotal role in effective treatments. In this study, we evaluated the effects of extracellular vesicles from human adipose-derived mesenchymal stem cells (AdMSC-EVs) on CECs. Firstly, colony formation assays showed that the colony-forming efficiency (CFE) of CECs significantly increased in the presence of AdMSC-EVs. Then we demonstrated that AdMSC-EVs accelerated migration of CECs in a scratch assay, whereas the proliferation of CECs was suppressed by AdMSC-EVs in cell proliferation assay. RNA Sequencing (RNA-Seq) analysis of CECs implied that AdMSC-EVs maintained the stemness, as well as improved epithelial-mesenchymal transition (EMT). Furthermore, having identified the six top microRNAs (miRNAs) of AdMSC-EVs, CEC transfection with those miRNA mimics, indicated that miR-25, miR-191, and miR-335 were the most effective molecules for improving stemness and EMT. Taken together, our findings indicated that AdMSC-EVs can enhance stemness and EMT of CECs, and AdMSC-EV effects are exerted by the contained miRNAs. RNA-Seq analysis of CECs from control group and AdMSC-EV-treated groups (at concentration of 30 μg/ml and 120 μg/ml). Three biological replicates in each group.