Background
Mesenchymal stem cells (MSCs) can migrate to tissue injury sites where they can induce multipotential differentiation and anti-inflammation effects to treat tissue injury. When traditional therapeutic
Conclusions
MSCs overexpressing HNF-4α exerted good therapeutic effects against mouse liver cirrhosis due to an enhanced anti-inflammatory effect. Gene modification is likely a promising method for improving the effects of cell therapy.
Methods
Carbon tetrachloride (CCl4) was used to establish a mouse liver cirrhosis model. Enhanced green fluorescence protein (EGFP) and hepatocyte nuclear factor-4α (HNF-4α) overexpression adenoviruses were used to modify MSCs. Three weeks after liver injury induction, mice were injected with bone marrow MSCs via their tail vein. The mice were then sacrificed 3 weeks after MSC injection. Liver injury was evaluated by measuring glutamic-pyruvic transaminase (ALT) and glutamic oxalacetic transaminase (AST) levels. Histological and molecular evaluations were performed to study the mechanisms.
Results
We found that HNF-4α-overexpressing MSCs had a better treatment effect than unmodified MSCs on liver cirrhosis. In the CCl4-induced mouse liver injury model, we found that HNF-4α-MSCs reduced inflammation in the liver and alleviated liver injury. In addition, we found that HNF-4α promoted the anti-inflammatory effect of MSCs by enhancing nitric oxide synthase (iNOS) expression, which was dependent on the nuclear factor kappa B (NF-κB) signalling pathway. Conclusions: MSCs overexpressing HNF-4α exerted good therapeutic effects against mouse liver cirrhosis due to an enhanced anti-inflammatory effect. Gene modification is likely a promising method for improving the effects of cell therapy.