title: Repair and regeneration of tracheal surface epithelium and submucosal glands in a mouse model of hypoxic-ischemic injury.
abstract: OBJECTIVE
  The heterotopic syngeneic tracheal transplant mouse model is an acute hypoxic-ischemic injury model that undergoes complete repair and regeneration. We hypothesized that the repair and regeneration process of the surface epithelium and submucosal glands would occur in a reproducible pattern that could be followed by the expression of specific markers of epithelial cell types.
  
  
  METHODS
  We used the syngeneic heterotopic tracheal transplant model to develop a temporal and spatial map of cellular repair and regeneration by examining the tracheal grafts at post-transplant days 1, 3, 5, 7, 10 and 14. We used pulsed BrdU and immunofluorescent staining to identify and follow proliferating and repairing cell populations.
  
  
  RESULTS
  We confirmed the reproducibility of the injury and repair in the model and we found a distinct sequence of reappearance of the various stem/progenitor and differentiated cell populations of the tracheal surface epithelium and submucosal glands. In the initial phase, the basal and duct cells that survived the injury proliferated to re-epithelialize the basement membrane with K5 and K14 expressing cells. Then these cells proliferated further and differentiated to restore the function of the epithelium. During this repair process, TROP-2 marked all repairing submucosal gland tubules and ducts. Non-CCSP-expressing serous cells were found to differentiate 4-5 days before Clara, mucus and ciliated cells.
  
  
  CONCLUSIONS
  Improving our understanding of the reparative process of the airway epithelium will allow us to identify cell-specific mechanisms of repair that could be used as novel therapeutic approaches for abnormal repair leading to airway diseases.
authors.affiliation: Department of Pediatrics, Mattel Children's Hospital, Los Angeles, California, USA.
authors.forename: Ahmed E
authors.initials: AE
authors.lastname: Hegab
authors.forename: Derek W
authors.initials: DW
authors.lastname: Nickerson
authors.forename: Vi Luan
authors.initials: VL
authors.lastname: Ha
authors.forename: Daphne O
authors.initials: DO
authors.lastname: Darmawan
authors.forename: Brigitte N
authors.initials: BN
authors.lastname: Gomperts
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D000860:Hypoxia / Q000473:pathology*; D007511:Ischemia / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012038:Regeneration; D020545:Respiratory Mucosa / Q000473:pathology / Q000502:physiology*; D014132:Trachea / Q000098:blood supply* / Q000473:pathology / Q000502:physiology*