Antioxidant preconditioning enhances adipose tissue-derived stem cell therapy by increasing intrahepatic engraftment for liver fibrosis

Abstract

Introduction: Although it has been pre-clinically suggested that adipose-derived mesenchymal stem cells (ADSC)-based therapy can effectively treat liver cirrhosis, the hepatic engraftment of ADSC is still extremely low, which affects the clinical translation of ADSC for liver cirrhosis treatment. Method: ADSCs were treated with hydrogen peroxide to induce cell stress. Antioxidants, including reduced glutathione and melatonin were co-treated to examine their protective effects and mechanisms on stem cell damage. Liver fibrosis model was also established to test the transplantation efficacy of ADSCs with or without antioxidants pre-incubation. Result: Our data showed that precondition of antioxidants synergistically enhances the anti-stress ability of ADSCs induced by hydrogen peroxide in vitro. We found that preconditioning with antioxidants significantly improves therapeutic efficacy of ADSCs transplantation in liver fibrosis mice, including ameliorating histological damage, oxidative stress, inflammation and fibrosis. In addition, we also found that preconditioned with antioxidants increases intrahepatic engraftment of ADSCs through reducing the hepatic content of NOXs and ROS both in vitro and in vivo. Conclusion: These findings suggested that antioxidant preconditioning can enhance ADSC-based therapy for liver fibrosis via in increasing hepatic engraftment of ADSCs, which may through suppressing NOXs/ROS signaling.