Normal growth of the fetal lung is dependent on fetal breathing movements. We have previously reported that an intermittent strain, which simulates normal fetal breathing movements, stimulates DNA synthesis and cell division of mixed fetal rat lung cells maintained in organotypic culture. To examine which cell type is responding to mechanical strain and to investigate whether the effects of strain on cell proliferation and mechanotransduction are affected by tissue architecture, we isolated fetal lung cells and subjected them to intermittent strain either as two-dimensional monolayer cultures or as three-dimensional organotypic cultures. Strain enhanced DNA synthesis of mixed cells, epithelial cells, and fibroblasts when cultured in a three-dimensional configuration. In contrast, no stimulatory effect on cell proliferation was observed when cells were strained as monolayer cultures. Intracellular signals, induced by strain, and cell morphology also varied depending on the culture conditions. These results suggest that mechanical strain stimulates the proliferation of both epithelial cells and fibroblasts and that the response of fetal lung cells to mechanical strain in vitro depends on cellular architecture.

The mammalian lung develops from an endodermal tube, derived from an invagination of the primitive foregut, entering the splanchnic mesoderm. This embryonic stage is followed by the pseudoglandular stage of sequential tubular bifurcations. In the subsequent canalicular stage, there is vascularization of the developing lung, which is followed by the saccular stage of acinar development (1). Because lung organogenesis involves cell proliferation, migration, and differentiation, the ontogenic sequence of these events in lung momhonenesis needs to be well coordi---

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