Adenovirus-mediated HIF-1α gene transfer promotes repair of mouse airway allograft microvasculature and attenuates chronic rejection

Targeting complement component 5a promotes vascular integrity and limits airway remodeling

“…Further, the simultaneous loss of complement C3 and C5a activity is sufficient to completely prevent airway ischemia, even in the absence of other immunosuppression. Preservation of blood flow in the allograft is highly correlated with maintenance of normal airway architecture (5,6,8), and C5a-inhibited C3 −/− recipients of tracheal allografts maintain normal airway architecture as defined by relatively little subepithelial fibrosis and normal pseudostratified epithelium.…”

“…hypoxia | chronic rejection | alloimmunity | fibrosis | bronchiolitis obliterans syndrome M icrovascular loss during acute rejection episodes causes local tissue ischemia and probably contributes to fibrotic remodelling and organ dysfunction in transplant recipients (1)(2)(3)(4)(5)(6). Lung transplant recipients may be especially vulnerable to this sort of injury because the bronchial arteries, the principal source of oxygenated blood in airways, are not usually reanastomosed at the time of surgery.…”

Models of Lung Transplant Research: a consensus statement from the National Heart, Lung, and Blood Institute workshop

“…A more limited repopulation of donor-derived cells can be observed in vivo using the mouse OTT model. This line of study may have value in determining how both destructive and reparative processes occur through the migration of cell populations from the recipient to the donor (77,80,83). OTT also facilitates lineage fate mapping studies to track the movement and transformation of various cell types in the allograft recipient (83)(84)(85).…”

“…This line of study may have value in determining how both destructive and reparative processes occur through the migration of cell populations from the recipient to the donor (77,80,83). OTT also facilitates lineage fate mapping studies to track the movement and transformation of various cell types in the allograft recipient (83)(84)(85). The mouse orthotopic lung transplant model also holds promise as an effective platform for evaluating the relative contribution of recipient cells in both the disease and repair of small airways and pulmonary parenchyma.…”

“…Although obliterative lesions are not observed, OTTs develop lymphocytic bronchitis (a large airway precursor of BOS) as well as subepithelial fibrosis (103). Findings from the OTT studies have been cautiously extrapolated to explain how occlusive fibrosis may evolve following rejection in higher generation bronchioles (77,80,83,104,105).…”