Mesenchymal determination of mechanical strain-induced fetal lung cell proliferation

Fetal breathing movements play an important role in normal fetal lung growth. We have previously shown that an intermittent mechanical strain regimen (60 cycles/min, 15 min/h), simulating normal fetal breathing movements, stimulated growth of mixed fetal rat lung cells in organotypic culture. In the present study, we examined the individual responses of the two major fetal lung cell types, fibroblasts and epithelial cells, to mechanical strain. Also, we investigated the effect of mesenchymal-epithelial interactions on strain-induced cell proliferation during fetal lung development. Fibroblasts and epithelial cells from day 18 to day 21 fetal rat lung (term = 22 days), cultured alone or as various recombinants, were subjected to either a 48-h static culture or to strain, and DNA synthesis was measured. Both cell types responded individually to strain with enhanced DNA synthesis throughout late fetal lung development. Independent of the recombination ratio, there was no additive response to strain when fibroblasts and epithelial cells from the same gestation were recombined. In contrast, strain-induced DNA synthesis was suppressed when cells from different gestations were recombined. The ontogenic response pattern of recombinants to mechanical strain was similar to that of fibroblasts but not of epithelial cells. Strain-induced proliferation increased and peaked at the early canalicular stage of lung development at 19 days of gestation and declined thereafter. We conclude that strain-enhanced growth of the fetal lung is gestation dependent and that the gestational response to mechanical force is regulated by the mesenchyme.