title: N-acetylcysteine-pretreated human embryonic mesenchymal stem cell administration protects against bleomycin-induced lung injury.
abstract: BACKGROUND
  The transplantation of mesenchymal stem cells (MSCs) has been reported to be a promising approach in the treatment of acute lung injury. However, the poor efficacy of transplanted MSCs is one of the serious handicaps in the progress of MSC-based therapy. Therefore, the purpose of this study was to investigate whether the pretreatment of human embryonic MSCs (hMSCs) with an antioxidant, namely N-acetylcysteine (NAC), can improve the efficacy of hMSC transplantation in lung injury.
  
  
  METHODS
  In vitro, the antioxidant capacity of NAC-pretreated hMSCs was assessed using intracellular reactive oxygen species (ROS) and glutathione assays and cell adhesion and spreading assays. In vivo, the therapeutic potential of NAC-pretreated hMSCs was assessed in a bleomycin-induced model of lung injury in nude mice.
  
  
  RESULTS
  The pretreatment of hMSCs with NAC improved antioxidant capacity to defend against redox imbalances through the elimination of cellular ROS, increasing cellular glutathione levels, and the enhancement of cell adhesion and spreading when exposed to oxidative stresses in vitro. In addition, the administration of NAC-pretreated hMSCs to nude mice with bleomycin-induced lung injury decreased the pathological grade of lung inflammation and fibrosis, hydroxyproline content and numbers of neutrophils and inflammatory cytokines in bronchoalveolar lavage fluid and apoptotic cells, while enhancing the retention and proliferation of hMSCs in injured lung tissue and improving the survival rate of mice compared with results from untreated hMSCs.
  
  
  CONCLUSIONS
  The pretreatment of hMSCs with NAC could be a promising therapeutic approach to improving cell transplantation and, therefore, the treatment of lung injury.
authors.affiliation: Department of Respiratory Medicine, Shanghai Sixth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.forename: Wu-Gang
authors.initials: WG
authors.lastname: Zhou
authors.forename: Xiao-Can
authors.initials: XC
authors.lastname: Guo
authors.forename: Min-Juan
authors.initials: MJ
authors.lastname: Wu
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Xu
authors.forename: Jun-feng
authors.initials: JF
authors.lastname: Jiang
authors.forename: Ce
authors.initials: C
authors.lastname: Shen
authors.forename: Hou-Qi
authors.initials: HQ
authors.lastname: Liu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D000975:Antioxidants / Q000378:metabolism; D001761:Bleomycin / Q000009:adverse effects*; D002470:Cell Survival; D053595:Embryonic Stem Cells / Q000187:drug effects*; D006801:Humans; D008171:Lung Diseases / Q000139:chemically induced* / Q000517:prevention & control; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D051379:Mice; D008819:Mice, Nude; D017382:Reactive Oxygen Species
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D017382:Reactive Oxygen Species; D001761:Bleomycin; D000111:Acetylcysteine