CoQ10 enhances the efficacy of airway basal stem cell transplantation on bleomycin-induced idiopathic pulmonary fibrosis in mice

Abstract

Background: Recent studies have demonstrated that airway basal stem cells (BCs) transplantation can ameliorate bleomycin-induced idiopathic pulmonary fibrosis (IPF) through lung regeneration promotion. However, BCs under oxidative stress in the alveolar microenvironment are poor in survival, causing unsatisfied efficacy of BCs transplantation. In this study, we investigated whether Coenzyme Q10(CoQ10) counteracts oxidative stress in the alveolar microenvironment, thus improved the efficacy of BCs transplantation for IPF treatment. Methods: The protective effects of CoQ10 on H2O2-induced BCs apoptosis and cytoplasmic reactive oxygen species (ROS) level were tested by flow cytometry in vitro. The therapeutic effects of BCs combined with CoQ10 were compared to a single BCs transplantation protocol in IPF treatment after 2 weeks and were evaluated by parameters including changes of body weight and survival rate, as well as various levels of pulmonary inflammation, α-SMA expression and hydroxyproline (HYP) in IPF mouse lung tissues. Results: CoQ10 preincubation with BCs (10 mM, 24 h) significantly reduced the late apoptosis of BCs and the number of oxidative stressful BCs as a result of H2O2 stimulation (1 mM, 6 h) in vitro. IPF mouse model was constructed through bleomycin (5 mg/kg) intratracheal instillation. Bleomycin-induced IPF mice showed weight loss continuously and mortality increased progressively during modeling. Serious pulmonary inflammatory cell infiltration, collagen fiber proliferation, and collagen protein deposition were observed in lung tissues of IPF mice. Though BCs transplantation alone improved indicators above in bleomycin-induced IPF mice to some extent, the combination with CoQ10 improved the transplantation efficacy and obtained better therapeutic effects. Conclusion: CoQ10 blocked H2O2-induced apoptosis of BCs and ROS production in vitro, and enhanced the efficacy of BCs transplantation against bleomycin-induced IPF in mice.