Liver fibrosis is an excessive wound healing process that occurs in response to liver damage depending on underlying aetiologies. Currently, there are no effective
therapies and FDA-approved
therapeutics for the treatment of
liver fibrosis except
liver transplantation. Multipotent adipose-derived stem cells (ADSCs) have received significant attention as regenerative medicine for
liver fibrosis owing to their advantages over stem cells with other origins. However, intrinsic limitations of stem cell
therapies, such as cellular rejection and
tumor formation, have impeded clinical applications of the ADSC-based liver
therapeutics. To overcome these problems, the extracellular nanovesicles (ENVs) responsible for the
therapeutic effect of ADSCs (A-ENVs) have shown considerable promise as cell-free
therapeutics for
liver diseases. However, A-ENVs have not been used for the treatment of intractable chronic
liver diseases including
liver fibrosis and
cirrhosis. Therefore, in this study, we investigated the in vitro and in vivo antifibrotic efficacy of A-ENVs in
thioacetamide-induced
liver fibrosis models. A-ENVs significantly downregulated the expression of fibrogenic markers, such as
matrix metalloproteinase-2, collagen-1, and alpha-smooth muscle actin. The systemic administration of A-ENVs led to high accumulation in fibrotic liver tissue and the restoration of liver functionality in
liver fibrosis models through a marked reduction in α-SMA and
collagen deposition. These results demonstrate the significant potential of A-ENVs for use as extracellular nanovesicles-based
therapeutics in the treatment of
liver fibrosis and possibly other intractable chronic
liver diseases.