Bronchiolitis obliterans (BO) is a major problem in lung transplantation, but a better mouse model to study the onset of disease will help with the development of therapies, according to the American Journal of Respiratory and Critical Care Medicine.
In a study led by Angela Panoskaltsis-Mortari, PhD, University of Minnesota, mice were lethally conditioned and given a rescue dose of T-cell–depleted, allogeneic bone marrow (BM) supplemented with a sublethal dose of allogeneic T cells.
At 2 months post–BM transplant, the lungs had extensive perivascular and peribronchiolar inflammation consisting of CD4+ T cells, CD8+ T cells, B cells, macrophages, neutrophils, and fibroblasts. In contrast to the acute model, histology showed airway obstruction consistent with BO.
Although the lung had severe allogeneic BM transplant–mediated disease, there was only mild to moderate graft-versus-host disease in liver, colon, skin, and spleen. High wet/dry weight ratios and elevated hydroxyproline were seen, consistent with pulmonary edema and fibrosis.
The researchers deemed the new mouse model useful for the study of BO associated with late post–hematopoietic stem cell transplant onset and chronic graft-versus-host disease, which also leads to poor outcome in the lung transplant setting.
To view abstract, click here.