Submersion culture of the intact fetal lung.

Intact whole lungs from 14 d rat fetuses were explanted to organ culture and maintained fully submerged in medium or positioned at the gas-fluid interface. Striking differences were observed in the morphological development of submersion cultured and interface cultured explants after 7 d in vitro. Submersion cultured lung developed as an expanded hollow organ, whereas the tissue of interface cultures was glandular in appearance and attenuated against the culture substrate. This difference in the development of the cultured lung may be attributed to the influence of surface tension forces at the gas-fluid interface versus the fluid immersed environment. In submersion culture the fetal lung followed a unique pattern of morphogenetic development. Under these culture conditions the lung expanded in three dimensions and retained its discrete lobar structure. The primitive bronchial epithelial tree of the fetal lung at explantation exhibited substantial histoarchitectural changes in vitro. Progressive branching of the epithelium into the surrounding lung mesenchyme gave rise to a pulmonary parenchyma bearing characteristics of the presumptive alveolar region of the late gestation fetal lung. The epithelium consisted predominantly of large, glycogen rich cuboidal cells interspersed with numerous structurally differentiated type II cells, containing lamellar bodies. The pulmonary parenchyma of the submersion cultured explant occupied a narrow margin of the lung wall, surrounding a large central lumen. This unique form of the cultured lung made it possible to examine the pulmonary epithelium by scanning electron microscopy. Data from the present study suggest that submersion culture of the intact fetal lung may provide a useful model system for study of the maturation of epithelial cell surface features during pulmonary development.