Adipose derived mesenchymal stem cell-seeded regenerated silk fibroin scaffolds reverse liver fibrosis in mice†

Abstract

Liver fibrosis (LF) is an important process in the progression of chronic liver disease to cirrhosis. We have previously demonstrated that a regenerated silk fibroin scaffold loaded with adipose-derived stem cells (RSF + ADSCs) can repair acute liver injury. In this study, we established a chronic LF animal model using carbon tetrachloride (CCl₄) and a high-fat diet. We then investigated the liver repair capacity after transplanting RSF + ADSC scaffolds and RSF scaffolds onto the liver surface of mice. Compared with the control group, the concentrations of ALT and AST in the serum were significantly reduced in the RSF and RSF + ADSC groups. HE staining and Masson trichrome staining revealed a decrease in the SAF score in both the RSF and RSF + ADSC groups. Meanwhile, the biomarkers of blood vessels and bile ducts, such as CD34, ERG, muc1, and CK19, were significantly elevated in the RSF + ADSC group. Finally, transcriptome analysis showed that the PPAR signaling pathway, which inhibits liver fibrosis, was significantly upregulated in both the RSF and RSF + ADSC groups. Our study suggests that, compared with RSF scaffolds alone, RSF + ADSCs have a significant repair effect on chronic LF in mice.