Heterotopic tracheal transplantation animal model of bronchiolitis obliterans: A reproducible model

Background: Chronic rejection or bronchiolitis obliterans (BO) is the main cause of morbidity and mortality 1 year after lung transplantation. The objective of this study was to develop a reproducible animal model that mimics the typical histological findings in human BO after lung transplantation. Material/Methods: We used 2 rat strains - Lewis (L) and Wistar (W) - and transplanted a segment of donor trachea into each recipient. The animals were divided into 2 groups: 1) donor and recipient of the same strain (W-W), and 2) donor and recipient of different strains (L-W). From each group, we created 4 subgroups examined at different time-points after transplantation (7, 14, 21, and 28 days). Variables were: degree of narrowing of the tracheal lumen, histological findings classified into 1 of 5 patterns, location of the ink (green or black), and presence of foreign body granuloma. Results: In the W-W group, we observed a gradual onset of fibrosis, notable at 21 and 28 days post-implant. In the L-W group, obliteration of the tracheal lumen was observed in all animals, with acute inflammation by day 7, and fibrosis from then on, loose fibrosis by day 14, and frank fibrosis on days 21 and 28. Green ink was observed in vascular structures, located in granulation tissue in the early phases of the BO-type lesion, then the staining becoming less clear as the histological features developed towards frank fibrosis. This trend was seen in both groups. Conclusions: The obliteration and fibrosis are more extensive if the donor and recipient are from different strains (L-W). Histological findings in the L-W group corresponded to progressive fibrosis until day 21.