Exosomal miR-183-5p from human hepatocyte-derived liver progenitor-like cells promotes liver regeneration during acute liver failure

Hepatocyte-derived liver progenitor-like cells (HepLPCs) can reversibly differentiate into mature hepatocytes and play important roles in liver regeneration following acute liver failure. However, the mechanisms by which HepLPCs exert these regulatory effects are unclear. Herein, we report that HepLPCs participate in reinitiating liver regeneration and improving survival during acute liver failure, at least in part, via miRNA-183-5p, which is released from HepLPCs in extracellular vesicles. Thus, these findings may identify novel targets and strategies for the treatment of acute liver failure. HepLPC-derived extracellular vesicles (HepLPC-EVs) were isolated from conditioned media and subjected to microRNA (miRNA) sequencing analysis. Primary human hepatocytes were treated with EVs or miRNA mimics and/or inhibitors. C57BL/6J mice were intraperitoneally injected with carbon tetrachloride (CCl4) or acetaminophen (APAP) to induce ALF. These mice were then treated with EVs or a miRNA agomir.