Rationale - Limited in vivo models exist to investigate the lung airway epithelial role in repair, regeneration, and pathology of chronic lung diseases. Herein, we introduce a novel animal model in asthma - a xenograft system integrating a differentiating human asthmatic airway epithelium with an actively remodeling rodent mesenchyme in an immunocompromised murine host. Methods - Human asthmatic and non-asthmatic airway epithelial cells were seeded into decellularized rat tracheas. Tracheas were ligated to a sterile cassette and implanted subcutaneously in the flanks of nude mice. Grafts were harvested at two, four, or six weeks for tissue histology, fibrillar collagen, and TGFβ activation analysis. We compared immunostaining in these xenografts to human lungs. Results - Grafted epithelial cells generated a differentiated epithelium containing basal, ciliated, and mucus-expressing cells. By four weeks post-engraftment, asthmatic epithelia showed decreased numbers of ciliated cells and decreased E-cadherin expression compared to non-asthmatic grafts, similar to human lungs. Grafts seeded with asthmatic epithelial cells had three times more fibrillar collagen and induction of TGFβ isoforms at six weeks post-engraftment compared to non-asthmatic grafts. Conclusions - Asthmatic epithelium alone is sufficient to drive aberrant mesenchymal remodeling with fibrillar collagen deposition in asthmatic xenografts. Moreover, this xenograft system represents an advance over current asthma models in that it permits direct assessment of the epithelial-mesenchymal trophic unit.
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 July 2017.
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