Formation and Investigation of Cell-Derived Nanovesicles as Potential Therapeutics Against Chronic Liver Disease.

This study aims to offer a new therapeutic approach using cell-derived nanovesicles (cdNVs) to overcome the lack of effective treatments for liver fibrosis, a reversible chronic liver disease. To achieve this goal we established the formation and purification of cdNVs from untreated, quiescent-like, or activated LX-2 cells, an immortalized human hepatic stellate cell (HSC) line with key features of transdifferentiated HSCs. Analysis of the genotype and phenotype of naïve and transdifferentiated LX-2 cells activated through transforming growth factor beta 1 (TGF-β 1 ), following treatment with cdNVs, revealed a concentration-dependent fibrosis regression. The beneficial fibrosis-resolving effects of cdNVs are linked to their biomolecular corona. Liposomes generated using lipids extracted from cdNVs exhibit a reduced anti-fibrotic response in perpetuated LX-2 cells and show a reduced cellular uptake. However, incubation with soluble factors collected during purification results in a new corona, thereby restoring fibrosis regression activity. Overall, cdNVs display encouraging therapeutic properties, making them a promising candidate for the development of liver fibrosis resolving therapeutics. This article is protected by copyright. All rights reserved.