Study on the regulatory mechanism of differentiation and invasive ability of human endometrial stromal cells

子宫内膜是在月经周期较短的时间内重复增殖和脱落的特殊组织，在胚胎着床和维持妊娠中起着重要作用。在正常子宫中，子宫内膜间质细胞向宫腔内增殖，形成增殖期子宫内膜的功能层。在子宫内膜异位症中，与正常组织相邻的细胞是间质细胞，周围也存在免疫细胞。因此，研究子宫内膜异位症的发生发展机制，有必要对间质细胞的侵袭进行研究。在本研究中，我们在知情同意的情况下从子宫内膜组织中分离出子宫内膜间质细胞，并利用子宫内膜间质细胞侵袭实验模型分析了其侵袭机制及其调控因素。我们发现子宫内膜间质细胞在体外具有侵袭能力。激素、达那唑、蛋白酶抑制剂、细胞因子、非甾体抗炎药和抗整合素抗体对基质细胞侵袭率无明显影响，但与人外周血单个核细胞(PBMC)共培养时侵袭率增加。将这些因素加入到PBMC共培养模型中，未观察到明显的影响。提示正常子宫内膜间质细胞具有侵袭潜能，其侵袭受免疫细胞的影响，提示其可能参与了子宫内膜异位症的发生发展。

Endometrium is a special tissue that repeat proliferation and shedding in a short period of menstrual cycle and play a important role in embryo implantation and the maintenance of pregnancy. In normal uterus, endometrial stromal cells proliferate toward the uterine cavity and form a functional larer of proliferative phase of endometrium. In endometriosis, cells adjacent to normal tissue are stromal cells and immune cells also exist around them. So it should be important to investigate the invasion of stromal cells to study the progressive mechanism of endometriosis. In this study, we isolated endometrial sfromal cells from the endometrial tissue under informed consent and analyzed the invasive mechanism and its regulatory factors using the invasion assay model of endometrial stromal cells. We found that endometrial stromal cells have invasive ability in vitro. Invasion rate of stromal cells was not apparently changed with addition of agents such as steriod hormones, danazol, protease inhibitors, cytokines, NSAIDs and anti integrin antibody, however, the invasion was increased when cells were cultured with human peripheral blood mononuclear cells (PBMC). No apparent effects of those factors were observed when they were added in PBMC co-culture model. These findings demonstrate that normal endometrial stromal cells have invasive potential and those invasion were affected by immune cells, suggested to be involved in progress of endometriosis