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.