Endometrial Stromal Cells Regulate Epithelial Cell Growth in Vitro: a New Co-culture Model

The regulation of epithelial cell function and morphogenesis by the paracrine effectors from the mesenchyme or stroma has been well established using in-vivo studies. A more complete understanding of these relationships has been delayed due, in part, to a lack of appropriate co-culture models. In this study, we describe a co-culture model which demonstrates that normal paracrine relationships can be reconstituted in vitro and that human endometrial stromal cells regulate both growth and differentiation of primary human endometrial epithelial cells. Interesting differences in the proliferation of stromal and epithelial cells were noted in response to the basement membrane extract, Matrigel((R)). Exposure of stromal cells to Matrigel((R)) enhanced the paracrine capacity of these cells in vitro. When epithelial cells were co-cultured in contact with stromal cells embedded in Matrigel((R)), epithelial cell growth was inhibited by 65-80% compared to controls. Stromal cells in contact with Matrigel((R)) also regulated epithelial cell differentiation, as shown by induction of glycodelin expression. These co-culture studies show great promise as a method to investigate the cellular interactions between endometrial stromal and epithelial cells and their environment and to understand the molecular basis for the regulation of normal growth and differentiation of cells within complex tissues such as the endometrium.