Hypoxia-conditioned umbilical cord mesenchymal stem cell secretome attenuates hepatic fibrosis in a bile duct ligation model of biliary atresia.

Abstract

PURPOSE: Biliary atresia (BA) is a progressive fibro-inflammatory cholangiopathy and the leading cause of neonatal cholestasis and pediatric liver transplantation. Mesenchymal stem cell (MSC)-derived secretome has emerged as promising acellular alternative to cell therapy. This study evaluated the potential of hypoxia-conditioned umbilical cord MSC (HU-UCMSC) secretome in rat model of biliary fibrosis induced by bile duct ligation (BDL). METHODS: Twenty-four male Sprague-Dawley rats were randomized into six groups: Sham, BDL, BDL + vehicle, and BDL treated with HU-UCMSC secretome at doses of 100, 200, and 400 μL. Serum biochemical markers and hepatic gene expression were analyzed using photometry and RT-qPCR. Histopathology and fibrosis fraction area were evaluated by Sirius Red staining. RESULTS: HU-UCMSC secretome produced dose-dependent hepatoprotection, significantly reducing SGOT, SGPT, and total bilirubin levels compared with untreated BDL rats. Histologically, collagen deposition and fibrosis fraction area were markedly reduced. Gene expression analysis showed significant downregulation of PDGF, α-SMA, and TNF-α, with context-dependent modulation of TGF-β and VEGF. CONCLUSION: Hypoxia-conditioned UC-MSC secretome improved hepatic function and mitigated fibrosis in the BDL model through suppression of profibrotic and inflammatory mediators. These findings support HU-UCMSC secretome as a safe, cell-free therapeutic candidate for biliary atresia and related pediatric cholestatic liver diseases.