Adipose-Derived Stem Cell Treatment Induces Early-Term Hes1 Upregulation in a Sox9- and Notch1-Independent Manner in a Rat Model of Bile Duct Ligation

<b>Background/Objectives:</b> Bile duct ligation (BDL), characterized by marked inflammation and fibrosis, effectively mimics many clinical conditions and is a valuable tool for investigating biliary regeneration. Our objective was to clarify the therapeutic benefits of adipose-derived stem cell (ADSC) treatment and signaling pathways mediating regenerative processes in a rat model of BDL. <b>Methods:</b> The BDL model was performed on Sprague-Dawley rats, and ADSC was administered intrasplenically at a dose of 10⁶ cells per animal. Liver function tests, gene and protein expression analyses, histological evaluation, and immunohistochemistry staining were performed to assess liver function, signaling pathways, inflammation, and fibrosis. <b>Results:</b> ADSC treatment returned liver function to sham levels. ADSC upregulated the Hes1 gene and protein expression in the early and late term. Inflammation, fibrosis, and total damage scores were decreased following ADSC treatment compared with the control. Immunohistochemistry staining revealed higher CD90, CD44, and CD29 stem cell marker expression in the ADSC treatment group. <b>Conclusions:</b> ADSC administration reduced fibrosis and biliary damage and restored liver function, potentially in a manner mediated by upregulated Hes1 expression, supporting its promise in biliary regeneration.