Long-term maintenance of human distal airway epithelial cells in nude mice: a potentially useful model for the study of pulmonary carcinogenesis and lung cell biology.

We investigated whether the normal morphology of distal airway epithelial cells from adult human lungs could be maintained for long periods of time as xenografts in nude mice. Peripheral lung tissue obtained from normal regions of lungs resected for lung cancer was transplanted subcutaneously into nude mice. The implants were then retrieved at intervals from 2 to 26 weeks for light and electron microscopy, and for immunohistochemical examination. At 2 weeks, revascularization of the implants and replication of immature epithelial cells were observed. At 4 weeks and thereafter, the epithelium formed in the implants was almost mature and normal in appearance. Pseudostratified columnar epithelium composed of ciliated, mucus, and basal cells lined the larger airspaces, whereas the smaller airspaces including alveolar structures were generally lined with type II pneumocytes and occasionally with Clara cells. Normal alveoli with type I pneumocytes and capillary networks were rarely observed. The implants were maintained in the nude mice for as long as 26 weeks. Cytokinetic studies of the epithelial cells in the implants using immunocytochemical detection of incorporated bromodeoxyuridine revealed that an inverse relationship existed between the degree of maturation and the replicative capacity of the epithelial cells. It was also found that, even in the mature epithelium, a small fraction of the cells were undergoing DNA synthesis. Peripheral lung tissue xenografts in nude mice may provide an excellent in vivo model for the study of pulmonary carcinogenesis and also for the study of both the function and differentiation of human epithelial cells of the distal airways.