title: Infusion of mesenchymal stem cells protects lung transplants from cold ischemia-reperfusion injury in mice.
abstract: BACKGROUND
  Cold ischemia-reperfusion injury (IRI) is a major cause of graft failure in lung transplantation. Despite therapeutic benefits of mesenchymal stem cells (MSCs) in attenuating acute lung injury, their protection of lung transplants from cold IRI remains elusive. The present study was to test the efficacy of MSCs in the prevention of cold IRI using a novel murine model of orthotopic lung transplantation.
  
  
  METHODS
  Donor lungs from C57BL/6 mice were exposed to 6 h of cold ischemia before transplanted to syngeneic recipients. MSCs were isolated from the bone marrows of C57BL/6 mice for recipient treatment. Gas exchange was determined by the measurement of blood oxygenation, and lung injury and inflammation were assessed by histological analyses.
  
  
  RESULTS
  Intravenously delivered MSC migration/trafficking to the lung grafts occurred within 4-hours post-transplantation. As compared to untreated controls, the graft arterial blood oxygenation (PaO2/FiO2) capacity was significantly improved in MSC-treated recipients as early as 4 h post-reperfusion and such improvement continued over time. By 72 h, oxygenation reached normal level that was not seen in controls. MSCs treatment conferred significant protection of the grafts from cold IRI and cell apoptosis, which is correlated with less cellular infiltration, a decrease in proinflammatory cytokines (TNF-α, IL-6) and toll-like receptor 4, and an increase in anti-inflammatory TSG-6 generation.
  
  
  CONCLUSIONS
  MSCs provide significant protection against cold IRI in lung transplants, and thus may be a promising strategy to improve outcomes after lung transplantation.
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Tian
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Bai
authors.initials: B
authors.lastname: Zhang
authors.forename: Xiangchen
authors.initials: X
authors.lastname: Dai
authors.forename: Guang
authors.initials: G
authors.lastname: Li
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Li
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Caigan
authors.initials: C
authors.lastname: Du
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D050377:Cold Ischemia / Q000009:adverse effects*; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011014:Pneumonia / Q000209:etiology / Q000517:prevention & control; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; C493487:Tlr4 protein, mouse; C513057:Tnfaip6 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins