title: Angiopoietin-1 Modified Human Umbilical Cord Mesenchymal Stem Cell Therapy for Endotoxin-Induced Acute Lung Injury in Rats.
abstract: OBJECTIVE
  Angiopoietin-1 (Ang1) is a critical factor for vascular stabilization and endothelial survival via inhibition of endothelial permeability and leukocyte- endothelium interactions. Hence, we hypothesized that treatment with umbilical cord mesenchymal stem cells (UCMSCs) carrying the Ang1 gene (UCMSCs-Ang1) might be a potential approach for acute lung injury (ALI) induced by lipopolysaccharide (LPS).
  
  
  METHODS
  UCMSCs with or without transfection with the human Ang1 gene were delivered intravenously into rats one hour after intra-abdominal instillation of LPS to induce ALI. After the rats were sacrificed at 6 hours, 24 hours, 48 hours, 8 days, and 15 days post-injection of LPS, the serum, the lung tissues, and bronchoalveolar lavage fluid (BALF) were harvested for analysis, respectively.
  
  
  RESULTS
  Administration of fluorescence microscope confirmed the increased presence of UCMSCs in the injured lungs. The evaluation of UCMSCs and UCMSCs-Ang1 actions revealed that Ang1 overexpression further decreased the levels of the pro-inflammatory cytokines TNF-α, TGF-β₁, and IL-6 and increased the expression of the anti-inflammatory cytokine IL-10 in the injured lungs. This synergy caused a substantial decrease in lung airspace inflammation and vascular leakage, characterized by significant reductions in wet/dry ratio, differential neutrophil counts, myeloperoxidase activity, and BALF. The rats treated by UCMSCs-Ang1 showed improved survival and lower ALI scores.
  
  
  CONCLUSIONS
  UCMSCs-Ang1 could improve both systemic inflammation and alveolar permeability in ALI. UC-derived MSCs-based Ang1 gene therapy may be developed as a potential novel strategy for the treatment of ALI.
authors.affiliation: Department of Hematology, The Qilu Childrens' Hospital, Shandong University, Jinan, Shandong Province, P.R. China.|Department of Pediatrics, The Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Zhi Wei
authors.initials: ZW
authors.lastname: Huang
authors.affiliation: Department of Hematology, The Qilu Childrens' Hospital, Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, The Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Hematology, The Qilu Childrens' Hospital, Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Hai Yan
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Department of Hematology, The Qilu Childrens' Hospital, Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hematology, The Qilu Childrens' Hospital, Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Hematology, The Qilu Childrens' Hospital, Shandong University, Jinan, Shandong Province, P.R. China. 2598260466@qq.com.
authors.forename: Le Ling
authors.initials: LL
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, The Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China. lyssyl88@sina.com.
authors.forename: Xiu Li
authors.initials: XL
authors.lastname: Ju
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000628:therapy*; D042683:Angiopoietin-1 / Q000235:genetics*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D004731:Endotoxins; D015316:Genetic Therapy; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D016207:Cytokines; D004731:Endotoxins; C508609:IL10 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: Angiopoietin-1; acute lung injury; human umbilical cord mesenchymal stem cell