Abstract
The response of S-phase cells labelled with bromodeoxyuridine (BrdU) in sheep airways undergoing repair in response to endobronchial brush biopsy was investigated in this study. Separate sites within the airway tree of anaesthetised sheep were biopsied at intervals prior to pulse labelling with BrdU, which was administered one hour prior to euthanasia. Both brushed and spatially disparate unbrushed (control) sites were carefully mapped, dissected, and processed to facilitate histological analysis of BrdU labelling. Our study indicated that the number and location of BrdU-labelled cells varied according to the age of the repairing injury. There was little evidence of cell proliferation in either control airway tissues or airway tissues examined six hours after injury. However, by days 1 and 3, BrdU-labelled cells were increased in number in the airway wall, both at the damaged site and in the regions flanking either side of the injury. Thereafter, cell proliferative activity largely declined by day 7 after injury, when consistent evidence of remodelling in the airway wall could be appreciated. This study successfully demonstrated the effectiveness of in vivo pulse labelling in tracking cell proliferation during repair which has a potential value in exploring the therapeutic utility of stem cell approaches in relevant lung disease models.
Highlights
The lung is a relatively stable organ with low rates of cell turnover, in the airways where less than 5% of epithelial cells proliferate at any given point in time [1]
This study successfully demonstrated the effectiveness of in vivo pulse labelling in tracking cell proliferation during repair which has a potential value in exploring the therapeutic utility of stem cell approaches in relevant lung disease models
In order to bridge the gap between studies in small animals and man, a gap assumed on the basis of anatomical and physiological contrasts, we sought to characterise the airway wall repair response in sheep, a species of acknowledged relevance as a model for several lung diseases [9,10,11,12]
Summary
The lung is a relatively stable organ with low rates of cell turnover, in the airways where less than 5% of epithelial cells proliferate at any given point in time [1]. In order to bridge the gap between studies in small animals and man, a gap assumed on the basis of anatomical and physiological contrasts, we sought to characterise the airway wall repair response in sheep, a species of acknowledged relevance as a model for several lung diseases [9,10,11,12]. Such approach carries the additional advantage of potentially aligning perturbation and assay techniques with those relevant to clinical and veterinary clinical disciplines. It was necessary to ascertain whether the proliferative cell response characterised using BrdU was qualitatively consistent with that previously characterised by our group using this model
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