Liver-Targeted Fetal MSC-Derived Extracellular Vesicles: A Therapeutic Approach in a Mouse Model of Acute Hepatic Failure

Background Acute hepatic failure (AHF) is a rapid deterioration of hepatocellular function, which includes coagulopathy and hepatic encephalopathy and it is related with high mortality rate. To date, liver replacement is the sole successful procedure for AHF with limitations related to donor organ shortage and lifelong immunosuppressive therapy. Mesenchymal stromal/stem cell “secretome”, including extracellular vesicles (EVs), offers considerable advantages over intact cell-based applications, such as lack of immunogenicity, standard manufacturing, and storage. However, targeted delivery of EVs to the liver still remains challenging for clinical translation. Methods We developed a novel protocol to generate liver-targeted EVs by coating EVs from umbilical cord MSCs (UC-MSCs) with albumin. EVs were isolated using ultracentrifugation and subsequently surface-modified with albumin to enhance hepatic targeting. AHF was induced in mice using carbon tetrachloride (CCl₄). The therapeutic efficacy of the albumin-coated EVs was evaluated via serum biomarker measurements and live imaging. Results The albumin-coated EVs (ALB-EVs) demonstrated higher liver bioaccumulation and reduced biodistribution to the other organs compared to naive EVs. CCL ₄₋ induced AHF mice treated with liver specific EVs exhibited significantly decreased levels of aminotransferases and improved liver morphology and histological features. The entire protocol, from EV isolation to treatment, can be completed within one week using standard laboratory techniques. Conclusions This method provides an efficient, reproducible strategy for liver-targeted EV-based therapy in acute hepatic failure. Albumin-coated EVs represent a promising and scalable platform for developing noncellular therapeutics in regenerative medicine.