title: Induced pluripotent stem cells alleviate lung injury from mesenteric ischemia-reperfusion.
abstract: BACKGROUND
  Mesenteric ischemia-reperfusion (I/R) injury is a serious pathophysiologic process that can trigger the development of multiorgan dysfunction. Acute lung injury is a major cause of death among mesenteric I/R patients, as current treatments remain inadequate. Stem cell-based therapies are considered novel strategies for treating several devastating and incurable diseases. This study examined whether induced pluripotent stem cells (iPSCs) lacking c-myc (i.e., induced using only the three genes oct4, sox2, and klf4) can protect against acute lung injury in a mesenteric I/R mouse model.
  
  
  METHODS
  C57BL/6 mice were randomly divided into the following groups: sham/no treatment, vehicle treatment with phosphate-buffered saline, treatment with iPSCs, and treatment with iPSC-conditioned medium. The mice were subjected to mesenteric ischemia for 45 minutes followed by reperfusion for 24 hours. After I/R, the lungs and the ileum of the mice were harvested. Lung injury was evaluated by histology, immunohistochemistry, and analyses of the levels of inflammatory cytokines, cleaved caspase 3, and 4-hydroxynonenal.
  
  
  RESULTS
  The intravenously delivered iPSCs engrafted to the lungs and the ileum in response to mesenteric I/R injury. Compared with the phosphate-buffered saline-treated group, the iPSC-treated group displayed a decreased intensity of acute lung injury 24 hours after mesenteric I/R. iPSC transplantation significantly reduced the expression of proinflammatory cytokines, oxidative stress markers, and apoptotic factors in injured lung tissue and remarkably enhanced endogenous alveolar cell proliferation. iPSC-conditioned medium treatment exerted a partial effect compared with iPSC treatment.
  
  
  CONCLUSIONS
  When considering the anti-inflammatory, antioxidant, and antiapoptotic properties of iPSCs, the transplantation of iPSCs may represent an effective treatment option for mesenteric I/R-induced acute lung injury.
authors.affiliation: From the Institute of Clinical Medicine (C.-K.H.,H.-H.H.,S.-H.C.), Environmental and Occupational Health Science (S.-K.H.), Emergency and Critical Care Medicine (H.-C.S.,C.-H.L.), Pharmacy (S.-H.C.), or Physiology (L.-K.C.,C.-M.Y., C.-C.J.) and Department of Emergency Medicine (C.-K.H.,H.-H.H.,H.-C.S.,M.-S.H.,C.-H.L.), School of Medicine, National Yang-Ming University; Emergency Department (C.-K.H.,H.-H.H.,H.-C.S.,M.-S.H., C.-H.L.) and Department of Medical Research (S.-H.C.,C.-C.J.), Taipei Veterans General Hospital; Department of Education and Research (C.-C.J.), Taipei City Hospital, Taipei, Taiwan.
authors.forename: Chorng-Kuang
authors.initials: CK
authors.lastname: How
authors.forename: Sen-Kuang
authors.initials: SK
authors.lastname: Hou
authors.forename: Luen-Kui
authors.initials: LK
authors.lastname: Chen
authors.forename: Cheng-Ming
authors.initials: CM
authors.lastname: Yang
authors.forename: Hsien-Hao
authors.initials: HH
authors.lastname: Huang
authors.forename: Hsin-Chin
authors.initials: HC
authors.lastname: Shih
authors.forename: Mu-Shun
authors.initials: MS
authors.lastname: Huang
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
authors.forename: Chen-Hsen
authors.initials: CH
authors.lastname: Lee
authors.forename: Chi-Chang
authors.initials: CC
authors.lastname: Juan
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D057026:Induced Pluripotent Stem Cells; D000090062:Kruppel-Like Factor 4; D065666:Mesenteric Ischemia / Q000503:physiopathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D015427:Reperfusion Injury / Q000503:physiopathology / Q000628:therapy*
chemical_list: D016207:Cytokines; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4