Excessive extracellular matrix accumulation, primarily as a result of hepatic stellate cell activation, is a hallmark of hepatic fibrosis, a progressive outcome of chronic liver injuries. Recent research studies suggest that stem cells, hepatocytes, and extracellular vesicles may provide therapeutic advantages due to their anti-inflammatory, antioxidative, and regenerative activities. This study aimed to comparatively evaluate the therapeutic efficacy of these agents in a rat model of carbon tetrachloride (CCl₄)-induced hepatic fibrosis.

Liver fibrosis was induced in male Wistar rats via intraperitoneal CCl₄ injections for 8 weeks. Then the animals were intravenously administrated stem cells, hepatocytes, hepatocyte-derived exosomes, or stem cell-derived exosomes. Also, a fibrosis, a sham, a intact, and a PBS-treated group were consider the controls. After treatment, protein expression (alpha-smooth muscle actin (α-SMA), desmin), oxidative stress markers (superoxide dismutase, glutathione peroxidase, malondialdehyde), serum biochemical parameters (aspartate aminotransferase, alanine aminotransferase, glucose, uric acid, cholesterol, triglycerides), and fibrosis-related gene expression (matrix metalloproteinase 2 (MMP2), platelete-derived growth factor receptor beta (PDGFRB), transforming growth factor-beta (TGF-β), thymosin beta-10 (TMSB10) and transmembrane protein 176B (TMEM176B)) were assessed.

Significant liver damage, changed metabolic parameters, increased oxidative stress, and upregulated fibrosis markers were all observed in the fibrosis group. On the contrary, all treatments caused considerable improvements, though exosomes derived from stem cells demonstrated the most significant effects. Along with improved histopathological features, this group exhibited significant decreases in oxidative damage, liver enzymes, and profibrotic marker expression.

Liver fibrosis was considerably reduced by stem cells, hepatocytes, and particularly their exosomes. Exosomes made from stem cells demonstrated the strongest therapeutic effect, confirming their potential as a viable noncellular hepatic fibrosis treatment approach.