title: Engraftment of adult human lung tissue in nonobese diabetic/severe combined immunodeficient mice: a novel lung epithelial regeneration model.
abstract: OBJECTIVE
  Injury causes the disruption of homeostatic cell-cell interactions and epithelial regeneration is part of the threshold response. Due to the lack of a good animal model for the investigation of these mechanisms, the kinetics of cell proliferation after injury to the human respiratory tract are poorly understood.
  
  
  METHODS
  To create a better model of human bronchioloalveolar epithelial regeneration, we engrafted adult human lung tissue into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Then the lung tissue was studied at various times up to 20 weeks after implantation.
  
  
  RESULTS
  The xenografts of bronchiolar epithelium showed characteristic features, including positivity for specific human antigens, and extensive regeneration was observed within 8 weeks after implantation. In addition, a few alveolar type II epithelial cells expressing prosurfactant protein C were detected in some areas. The distal alveolar spaces were filled with protein-rich material and were markedly dilated. Abundantly ciliated secretory epithelium, which was similar to normal adult bronchiolar epithelium, was observed within 16 weeks after implantation in the mice. All of the human lung tissue specimens that were implanted subcutaneously into the backs of the mice developed well and remained viable for 20 weeks. Each type of adult human lung epithelial cell showed a different mode of proliferation. Bronchiolar epithelial cells proliferated earlier, with MIB-1 labeling of up to 20% of the cells in the grafts at 8 weeks, while alveolar type II cells proliferated later, with labeling of up to 5% of graft cells at 12 weeks.
  
  
  CONCLUSIONS
  This model seems to allow adult human lung epithelial regeneration to be investigated in vivo over the long term.
authors.affiliation: Pathology Division, National Cancer Center Research Institute East, Chiba, Germany.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yonou
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yokose
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Kanomata
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kamijo
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hasebe
authors.forename: Kanji
authors.initials: K
authors.lastname: Nagai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.forename: Akira
authors.initials: A
authors.lastname: Yamasaki
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hatano
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Makito
authors.initials: M
authors.lastname: Emura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
mesh_terms: D000368:Aged; D000818:Animals; D002455:Cell Division; D004848:Epithelium / Q000502:physiology* / Q000648:ultrastructure; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D016040:Lung Transplantation / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008854:Microscopy, Electron; D008875:Middle Aged; D023421:Models, Animal; D012038:Regeneration; D014183:Transplantation, Heterologous; D019737:Transplants