Induction of decidualization of endometrial stromal cells as a therapeutical approach for the treatment of endometriosis

诱导子宫内膜基质细胞蜕膜化作为治疗子宫内膜异位症的治疗方法

• 批准号: 323726627
• 负责人: Professorin Dr. Alexandra P. Bielfeld
• 金额: --
• 依托单位: Institut für Anatomie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/323726627?language=en
• 关键词: Induction; decidualization; endometrial; stromal; cells

Endometriosis is characterized by the presence of endometrial tissue in ectopic locations and leads to severe abdominal pain and subfertility. Moreover, current medical treatment is associated with undesirable side effects and high recurrence rates. Since endometrial stromal cells play a pivotal role in the establishment of this disease, and terminal differentiation (decidualization) of these cells has been shown to be impaired in endometriosis patients, induction of decidualization of ectopic endometrial stromal cells may be a promising target for innovative therapeutical approaches. Thus the aim of the project is to discover potential inductors of decidualization and apoptosis of endometrial stromal cells of endometriosis patients. Based on the finding that the progesterone receptor pathway as well as cAMP-mediated signalling is involved in induction of decidualization, compounds interacting with these pathways will be analyzed in regard to their potential to induce differentiation of endometrial stromal cells from women with and without endometriosis. Effective compounds and compound combinations will be evaluated in vitro using primary culture of endometrial stromal cells of both study groups. Thereafter, the most promising agents will be evaluated in an endometriosis mouse model in regard to their potential to induce decidualization of ectopic endometrial lesions in vivo. The respective effect on decidualization will be evaluated by morphologic parameters and by quantification of the decidualization marker prolactin. Moreover, the effect of these compounds on proliferation, apoptosis, and angiogenesis will be analyzed. The potency of the compounds tested on induction of decidualization and regression of lesions will be correlated to the receptor status of the endometrium of single patients, targeting on the development of individualized therapeutical approaches.

子宫内膜异位症的特征是异位内膜组织的存在，并导致严重的腹痛和不孕症。此外，目前的治疗与不良的副作用和高复发率有关。由于子宫内膜间质细胞在子宫内膜异位症的发生中起着关键作用，而且这些细胞的终末分化(蜕膜化)在子宫内膜异位症患者中受到损害，诱导异位内膜间质细胞的蜕膜化可能是创新治疗方法的一个有前途的靶点。因此，该项目的目的是寻找子宫内膜异位症患者子宫内膜间质细胞蜕膜化和凋亡的潜在诱导物。基于孕激素受体途径和cAMP介导的信号通路参与蜕膜化诱导的发现，将分析与这些途径相互作用的化合物诱导患有和不患有子宫内膜异位症的妇女的子宫内膜间质细胞分化的潜力。有效的化合物和化合物组合将使用两个研究组的子宫内膜间质细胞的原代培养进行体外评估。此后，最有希望的药物将在子宫内膜异位症小鼠模型中进行评估，以确定它们在体内诱导异位内膜病变蜕膜化的可能性。将通过形态参数和蜕膜化标志物催乳素的定量来评估各自对蜕膜化的影响。此外，还将分析这些化合物对细胞增殖、细胞凋亡和血管生成的影响。这些化合物在诱导蜕膜化和皮损消退方面的效力将与单个患者子宫内膜的受体状态相关，旨在开发个性化的治疗方法。