miR-26b-modified human umbilical cord mesenchymal stem cells exhibit enhanced anti-fibrotic efficacy in a mouse model of hepatic fibrosis.

OBJECTIVE: Conventional human umbilical cord mesenchymal stem cells (HUCMSCs) show insufficient liver homing and limited therapeutic efficacy against hepatic fibrosis. This work aimed to construct miR-26b-overexpressing HUCMSCs (Ad-26b-HUCMSCs) and explore their anti-fibrotic capacity and underlying mechanisms. METHODS: Adenovirus was applied to achieve miR-26b overexpression in HUCMSCs. CCK-8, Transwell and flow cytometry assessed cell viability, migration and apoptosis in vitro. A CCl₄-induced mouse hepatic fibrosis model was established, with four animal groups receiving sham treatment, PBS, Ad-HUCMSCs or Ad-26b-HUCMSCs via tail vein injection. Liver function, serum cytokines, liver histopathology, cell homing and hepatic marker expression were measured 28 days post-transplantation. RESULTS: miR-26b modification significantly enhanced HUCMSC viability, migratory ability and liver engraftment without increasing apoptosis. Ad-26b-HUCMSCs markedly lowered serum ALT, AST, IL-1β, IL-6 and TGF-β, relieved hepatic collagen deposition, suppressed α-SMA and TNF-α, and elevated AFP, ALB and CK18 expression in injured liver compared with unmodified HUCMSCs. CONCLUSIONS: miR-26b overexpression improves the survival, liver-targeted migration and hepatic marker expression of HUCMSCs. Ad-26b-HUCMSCs exert potent anti-fibrotic effects, offering an optimized stem cell therapeutic strategy for hepatic fibrosis.