A Novel Humanized Model To Study the Development of Obliterative Airway Disease

Abstract

Purpose Different in vivo models have been developed to study the pathogenesis and treatment of obliterative airway disease (OAD). However, all in vivo models are limited by the fact that fibroproliferative lesions are from murine origin and there is the need for a humanized model to overcome the translational gap. Here we describe a novel technique to follow OAD development in human bronchi in vivo. Methods and Materials Human bronchi (diameter approx. 3mm) were transplanted into the tracheal position of immunocompetent (BN) or immunodeficient (RNU; lacking T cells) rats (total n=24) by end-to-end anastomosis. Grafts were harvested after 7 or 28 days post-transplantation. Histopathology and inflammatory cell infiltration was compared to human samples recovered from BOS patients (n=2). The kinetics of systemic host immune response and epithelial coverage was assessed and the origin of proliferating cells quantified. Results Cellular host response, as determined by the IFN-g-ELISPOT assay 7 days after transplantation was significantly stronger in the immunocompetent group (131±4 vs. 8±6 spots in the immunodeficient group, p Conclusions The human bronchus transplantation model imitates lesions and epithelial integrity of BOS patients and is therefore suitable to study the development of BOS in vivo.