Tissue-engineered endometrial model for the study of cell-cell interactions.

Endometrial stromal and epithelial cell cross talk is known to influence many of the dynamic changes that occur during the menstrual cycle. We modified our previous model and embedded telomerase-immortalized human endometrial stromal cells and Ishikawa adenocarcinoma epithelial cells in a collagen-Matrigel hydrogel to create a tissue-engineered model of the endometrium. Comparisons of single and cocultured cells examined communication between endometrial stromal and epithelial cells, which were cultured with 0 or 10 nmol/L 17β estradiol; conditioned medium was used to look at the production of paracrine factors. Using this model, we were able to identify the changes in interleukin 6 (IL-6) and active matrix metalloproteinase 2, which appear to be due to paracrine signaling and differences in transforming growth factor β1 (TGF-β1) that do not appear to be due to paracrine signaling. Moreover, IL-6, TGF-β1, and DNA content were also affected by the presence of estradiol in many of the tissues. These results indicate that paracrine and endocrine signaling are involved in human endometrial responses and support the use of coculture models to further investigate cell-cell and cell-matrix interactions.