A variety of animal models including dogs, rabbits, guinea pigs, hamsters, rats and mice, and different sources of injury (oxidants, cigarette smoke, mechanical injury, and viral or bacterial infections) have been developed. These models of airway epithelium injury and repair in vivo point to several common sequential processes of repair and epithelial regeneration, including the following: (1) spreading and migration of the basal cells neighbouring the wound, (2) rapid restoration of tight junctions, (3) pre-mitosis dedifferentiation followed by squamous metaplasia, (4) active mitosis leading to basal and mucous cell hyperplasia, followed by (5) progressive redifferentiation with the emergence of 'pre-ciliated' cells (a mixed phenotype of ciliated and mucous cells) and ciliogenesis, allowing the regeneration of a functional mucociliary epithelium .
Regeneration of the hamster tracheal epithelium after mechanical injury has demonstrated rapid re-epithelialization of the denuded epithelium and has shown that cell migration, rather than cell proliferation, occurs first . Epithelial cells at the border of the wounded area are able to dedifferentiate, spread and migrate over the denuded basement membrane to cover the deepithelialized area. Ramphal et al  have shown that, after infection with influenza virus, complete desquamation of the epithelium occurs within 3 days, whereas regeneration begins within 5 days and is completed in 2 weeks.
Of the three main airway epithelial cell types, basal and secretory cells are known to divide, whereas ciliated cells are considered to be terminally differentiated. Several investigations support the role of basal cells as progenitors [6,7,8,9]; others suggest that only secretory cells can regenerate a complete mucociliary epithelium .
Animal tracheal xenograft models have also been developed to analyse airway epithelium regeneration and to try to identify progenitor cell subpopulations involved in this process. Inducing a regeneration process in airway epithelial tissue, which is normally characterized by a low turnover, accelerates proliferation and differentiation.
Rat tracheas were denuded of their surface epithelium by repeated cycles of freezing and thawing, then seeded with adult rat tracheal epithelial cells and implanted subacutanenously into immunodeficient nude mice . Within a few days, the inoculated cells re-established an epithelial lining that was at first 'poorly differentiated' but then developed the features typical of the epithelium from which the cells originated. These poorly differentiated cells, which expressed markers of basal cells but not secretory or ciliated cells, seem to have a pivotal role in the regeneration-differentiation process. Secretory cells sorted by flow cytometry from the rat trachea seem to have a greater colony-forming efficiency than basal cells, and hence could be stem cells . Conversely, in other studies, basal cells elutriated from rabbit trachea acted as basal cells and gave rise to secretory and ciliated cell types in the host trachea .
Submucosal gland cells might also be important in the renewal of the airway epithelium. The group of S Randell and J Dorin  found a distinct population of cells expressing high levels of keratin gene and protein in the ciliated ducts of the murine trachea. Because injury is needed to recruit stem cells into division, they damaged the tracheal epithelium and analysed stem cell divisions by injecting bromodeoxyuridine during injury and repair. At 3 and 6 days after injury, bromodeoxyuridine-positive epithelial cells were present along the entire tracheal length in all cells (whether luminal, intermediate or basal cells). By 3 months after injury, the surface epithelium adjacent to gland openings contained bromodeoxyuridine-positive basal cells, suggesting the presence of a stem cell niche in the ciliated ducts. After the removal of surface epithelium, cells migrated from glands to repopulate the tracheal epithelial surface. These results are in agreement with those of Engelhardt's group, which has shown in the newborn ferret that the expression of Lef1 marks early submucosal gland progenitor cells .
All these studies in vivo suggest that several categories of stem cell and progenitor cell, including columnar, basal and ciliated duct cells, can participate in airway epithelium regeneration and renewal. Nevertheless, histological differences exist between human airways and those of other animal species, raising doubts as to the relevance of the latter as models. Mouse tracheal epithelium is composed mainly of ciliated and Clara cells, the latter being present only in human distal airways, and only a few submucosal gland cells are identified at the upper tracheal level in mice.