THE EFFECT OF GROWTH-FACTORS ON THE PROLIFERATION OF HUMAN ENDOMETRIAL STROMAL CELLS IN CULTURE

OBJECTIVE: Development of ectopic implants of endometriosis is associa ted with both an inflammatory response by macrophages and endometrial stromal cell proliferation. Macrophages are capable of releasing a var iety of inflammatory mediators, including growth factors. To assess th e impact of such factors on endometrial tissue, we have studied the ef fects of recombinant growth factors, fibroblast growth factor, epiderm al growth factor, transforming growth factor-alpha, and inflammation m ediators transforming growth factor-beta, and tumor necrosis factor-a on human endometrial stromal cell proliferation. STUDY DESIGN: Increas ing concentrations of these compounds were added to cultures of primar y, secondary, and long-term stromal cells and the cells were harvested at 24, 48, and 72 hours. RESULTS: Epidermal growth factor, transformi ng growth factor-alpha, transforming growth factor-beta, and fibroblas t growth factor induced a statistically significant, dose-dependent in crease in stromal cell thymidine uptake of 1.5- to fivefold. The cytok ine tumor necrosis factor had no effect alone, but the combination of fibroblast growth factor and tumor necrosis factor had a synergistic e ffect, increasing cell proliferation 25% to 84% over fibroblast growth factor alone. CONCLUSION: The stromal cell response to a wide range o f cell growth effectors and the potential of mediators like tumor necr osis factor-alpha to synergize suggest that such macrophage-secretory products may contribute to proliferation of endometrial implants in vi vo.