Formation and Investigation of Cell‐Derived Nanovesicles as Potential Therapeutics against Chronic Liver Disease

Abstract

AbstractA new therapeutic approach using cell‐derived nanovesicles (cdNVs) is offered here to overcome the lack of effective treatments for liver fibrosis, a reversible chronic liver disease. To achieve this goal 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 are established. Analysis of the genotype and phenotype of naïve and transdifferentiated LX‐2 cells activated through transforming growth factor beta 1, following treatment with cdNVs, reveals 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 antifibrotic 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.