title: IV delivery of induced pluripotent stem cells attenuates endotoxin-induced acute lung injury in mice.
abstract: BACKGROUND
  Induced pluripotent stem (iPS) cells are novel stem cell populations, but the role of iPS cells in acute lung injury (ALI) is not currently known. We investigated the effect of iPS cells in modifying the pathophysiology of endotoxin-induced ALI.
  
  
  METHODS
  Male C57BL/6 8- to 12-week-old mice were enrolled in this study. Mouse iPS cells were delivered through the tail veins of mice 4 h after intratracheal instillation of endotoxin. Lung histopathologic findings, the pulmonary levels of cytokines, and functional parameters were analyzed after either 24 h or 48 h.
  
  
  RESULTS
  More iPS cells integrated into the lungs of mice with ALI than those of the control mice, as demonstrated by in vivo radionuclide imaging and in vitro Hoechst-labeled fluorescent staining. iPS cells significantly diminished the histopathologic changes of ALI and the lung injury score. There was also a significant reduction in the activity of nuclear factor-κB (NF-κB) and neutrophil accumulation in the lung, confirmed by immunostaining, electrophoretic mobility shift assays, and the decrease of myeloperoxidase activity, in the iPS-cell-treated mice with ALI. These protective effects were not replicated by the control cell therapy with fibroblasts. iPS cells mediated a downregulation of the proinflammatory response to endotoxin (reducing tumor necrosis factor-α, IL-6, and macrophage inflammatory peptide-2). In addition, iPS cells rescued the hypoxemia and pulmonary function of ALI. Treatment with a conditioned medium of iPS cells showed effects similar to those of iPS cells, which may suggest the therapeutic benefits of iPS mediated by paracrine factors.
  
  
  CONCLUSIONS
  IV delivery of iPS cells provides a beneficial effect to attenuate the severity of endotoxin-induced ALI and improve physiologic impairment, which is partly mediated by a reduction in NF-κB activity and neutrophils accumulation. The conditioned medium of iPS cells demonstrated effects equal to those of iPS cells.
authors.affiliation: Department of Chest Medicine, Taipei Veterans General Hospital; Institute of Clinical Medicine, National Yang-Ming University.
authors.forename: Kuang-Yao
authors.initials: KY
authors.lastname: Yang
authors.affiliation: Department of Emergency Medicine, Taipei Veterans General Hospital; Institute of Clinical Medicine, National Yang-Ming University; Institute of Emergency and Critical Care Meicine, National Yang-Ming University.
authors.forename: Hsin-Chin
authors.initials: HC
authors.lastname: Shih
authors.affiliation: Department of Emergency Medicine, Taipei Veterans General Hospital; Institute of Clinical Medicine, National Yang-Ming University; Institute of Emergency and Critical Care Meicine, National Yang-Ming University.
authors.forename: Chorng-Kuang
authors.initials: CK
authors.lastname: How
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University; School of Medicine, National Yang-Ming University; Department of Medical Research and Education, National Yang-Ming University Hospital.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Surgery, Taipei Veterans General Hospital; School of Medicine, National Yang-Ming University.
authors.forename: Han-Shui
authors.initials: HS
authors.lastname: Hsu
authors.affiliation: Department of Surgery, Taipei Veterans General Hospital; School of Medicine, National Yang-Ming University.
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Yang
authors.affiliation: Department of Chest Medicine, Taipei Veterans General Hospital; School of Medicine, National Yang-Ming University.
authors.forename: Yu-Chin
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Chest Medicine, Taipei Veterans General Hospital; School of Medicine, National Yang-Ming University.
authors.forename: Reury-Perng
authors.initials: RP
authors.lastname: Perng
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University; Shin Kong Wu Ho-Su Memorial Hospital and Fu-Jen Catholic University, National Taiwan University, Taipei, Taiwan, China.
authors.forename: Chi-Hsien
authors.initials: CH
authors.lastname: Peng
authors.affiliation: Department of Medical Research and Education, Taipei Veterans General Hospital; Department of Obstetrics and Gynecology, Taipei Veterans General Hospital; Institute of Clinical Medicine, National Yang-Ming University; School of Medicine, National Yang-Ming University.
authors.forename: Hsin-Yang
authors.initials: HY
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Taipei Veterans General Hospital; Institute of Oral Biology, National Yang-Ming University; School of Medicine, National Yang-Ming University.
authors.forename: Chia-Ming
authors.initials: CM
authors.lastname: Chang
authors.affiliation: Department of Chemistry, College of Science, National Taiwan University, Taipei, Taiwan, China.
authors.forename: Chung-Yuan
authors.initials: CY
authors.lastname: Mou
authors.affiliation: Department of Surgery, Taipei Veterans General Hospital; Institute of Clinical Medicine, National Yang-Ming University; Institute of Pharmacology, National Yang-Ming University; School of Medicine, National Yang-Ming University. Electronic address: kyyang@vghtpe.gov.tw.
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
mesh_terms: D055371:Acute Lung Injury / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000628:therapy*; D000704:Analysis of Variance; D000818:Animals; D001784:Blood Gas Analysis; D018920:Coculture Techniques; D016207:Cytokines / Q000032:analysis; D004731:Endotoxins; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D011877:Radionuclide Imaging; D012129:Respiratory Function Tests
chemical_list: D016207:Cytokines; D004731:Endotoxins; D016328:NF-kappa B