Decoding therapeutic roles of adipose tissue-derived stromal cells and their extracellular vesicles in liver disease

Acute and chronic liver damage are associated with severe pathogenic conditions, including loss of functional liver tissue (hepatocyte cell death), inflammation and fibrosis. Mesenchymal stromal cells (MSC) have therapeutic potential and, upon systemic infusion, they have the ability to home to the injured liver. MSC improve liver function and ameliorate fibrosis, rendering a promising therapeutic strategy for patients with end-stage liver disease. Despite the fact that MSC are able to differentiate into hepatocytes, especially in in vitro conditions, their therapeutic effect in acute and chronic liver disease are believed to be primarily based on paracrine signaling, mediated through the release of trophic factors and extracellular vesicles (EVs). Several trophic molecules have been indicated to convey the therapeutic effects of MSC, while the role of MSC-derived EVs has not yet been thoroughly investigated. EVs carry various regulatory nucleic acids and proteins and deliver their cargo into target cells. Cargo of EVs modulates key cellular processes in the recipient cells, such as transcription, post-transcriptional modification and signal transduction. In this thesis, we studied the therapeutic potential of EVs produced by human adipose tissue-derived MSC (ASC) in murine (in vivo), cellular (in vitro), and tissue (ex vivo) models of human acute and chronic liver disease