Biologically Intact Therapeutic Exosomes From Human Hepatic Progenitor Cells for Liver Diseases.

Abstract

The worldwide prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD) is rising significantly. However, effective treatment methods for these diseases are lacking, and using exosomes as a promising approach faces significant challenges due to their biological integrity. Here, we report the therapeutic effects of biologically intact exosomes derived from healthy hepatic cells in reducing lipids in cells affected by steatotic liver disease. We first obtained biologically intact exosomes, with a peak size of 30-200 nm and a round shape, as determined by CD63 and CD81 exosome markers, using the biologically intact exosome separation technology (BEST). We induced steatotic liver disease models containing lipid droplets in AML12 cells using oleic acid and ethanol, maintaining approximately 90% cell viability compared to normal hepatocytes. Furthermore, we verified the effectiveness of therapeutic exosomes containing two miRNAs (hsa-miR-122-5p and hsa-miR-27a-3p), which significantly reduced lipid accumulation by up to 92.7% in MASLD and 93.2% reduction in ALD at a dosage of 100 µg/mL of intact exosomes over 72 h. Ultimately, these findings highlight the potential of exosomes as a cell-free treatment for reversing steatotic liver diseases.