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

人子宫内膜基质细胞分化及侵袭能力调控机制研究

• 批准号: 13671708
• 负责人: TATSUMI Keiji
• 金额: $ 2.24万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671708/
• 关键词: endometrial stromal cells; invasion; endometriosis; peripheral blood mononuclear cells; DNA array

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

子宫内膜是一种特殊的组织，在短时间的月经周期内反复增殖和脱落，对胚胎着床和妊娠的维持起着重要作用。在正常子宫中，子宫内膜间质细胞向宫腔增殖，形成子宫内膜增殖期的功能层。在子宫内膜异位症中，与正常组织相邻的细胞是基质细胞，免疫细胞也存在于它们周围。因此，研究子宫内膜异位症的发生发展机制，有必要探讨基质细胞的侵袭情况。本研究在知情同意的情况下，从子宫内膜组织中分离子宫内膜间质细胞，利用子宫内膜间质细胞侵袭实验模型，分析其侵袭机制及其调控因素。我们发现子宫内膜间质细胞具有体外侵袭能力。加入类固醇激素、达那唑、蛋白酶抑制剂、细胞因子、非甾体类抗炎药和抗整合素抗体等对基质细胞的侵袭率无明显影响，但与人外周血单个核细胞（PBMC）共同培养时，基质细胞的侵袭率明显增加。在PBMC共培养模型中加入这些因素后，未观察到明显的影响。这些结果表明，正常子宫内膜间质细胞具有侵袭潜能，并且这些侵袭受到免疫细胞的影响，提示这些细胞参与了子宫内膜异位症的发生、发展

项目成果

Sato Y.: "Involvement of dipeptidyl peptidase IV in extravillous trophoblast invasion and differentiation"J Clin Endocrinol Metab.. 87. 4287-4296 (2002)

Sato Y.：“二肽基肽酶 IV 参与绒毛外滋养层侵袭和分化”J Clin Endocrinol Metab.. 87. 4287-4296 (2002)

Egawa H. et al.: "Peripheral blood mononuclear cells in early pregnancy promote invasion of human choriocarcinoma cell line, BeWo cells"Human Reproduction. 17(2). 473-480 (2002)

Ekawa H.等人：“妊娠早期外周血单核细胞促进人绒毛膜癌细胞系BeWo细胞侵袭人类生殖”。

Sato Y.: "Gonadotropin-induced expression of pancreatitis-associated protein-III mRNA in the rat ovary at the time of ovulation"J Clin Endocrinol Metab.. 174. 485-492 (2002)

Sato Y.：“排卵时大鼠卵巢中促性腺激素诱导的胰腺炎相关蛋白-III mRNA 的表达”J Clin Endocrinol Metab.. 174. 485-492 (2002)

Fujiwara H. et al.: "Acute elevation of plasma D-dimer levels associated with rupture of an ovarian endometriotic cyst: Case report"Human Reproduction. 18. 338-341 (2003)

Fujiwara H. 等人：“与卵巢子宫内膜异位囊肿破裂相关的血浆 D-二聚体水平急性升高：病例报告”人类生殖。

Nakayama T. et al.: "Human peripheral blood mononudear cells (PBMC) in early pregnancy promote embryo invasion in vitro: HCG enhances the effects of PBMC"Human Reproduction. 17(1). 207-212 (2002)

Nakayama T.等人：“妊娠早期人外周血单核细胞（PBMC）在体外促进胚胎侵袭：HCG增强PBMC对人类生殖的影响”。