Differentiation of rat intestinal epithelial cells is induced by organotypic mesenchymal cells in vitro.

Stromal-epithelial interaction is a potent driving force in the developing intestinal mucosa which ensures tissue specific cellular differentiation. The mechanisms involved are relevant to tissue renewal in adult organs yet they have not been elucidated because of the lack of appropriate in vitro models. In this study, we have investigated the interaction between intestinal mesenchymal and epithelial cells at the cellular level in vitro. Fetal rat intestinal epithelial cell colonies explanted in vitro on the 15th day of gestation, which failed to mature in plain monocultures, were reassociated in coculture with three different types of mesenchyme:fetal skin, gastric and intestinal mesenchyme. Only fetal epithelial cells cocultured with intestinal (homologous) mesenchyme acquired definite signs of differentiation within three to six days. These primitive epithelial cells were shown by electronmicroscopy to become highly polarized, connected by tight junctions and covered with a regular brush border. Three brush border enzymes were strongly expressed in homologous cocultures and their activity was sensitive to dexamethasone. In contrast, fetal epithelial cells cocultured with skin or stomach derived mesenchyme under identical conditions failed to differentiate in vitro: they remained flat, unpolarised and expressed only low enzyme activity. The unique potential of the small intestinal mesenchyme to promote intestinal epithelial differentiation is discussed.