Microphysiological modeling of Endometriosis

子宫内膜异位症的微生理学模型

• 批准号: 10816913
• 负责人: Ji-Yong Julie Kim
• 金额: $ 56.24万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-25 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10816913
• 关键词: Affect; Age; Area; Behavior; Biological Assay; Biological Models; Blood Cells; Cell Line; Cell physiology; Cells; Clinic; Communities; Control Groups; DNA analysis; Disease; Endometrial; Epithelial Cells; Etiology; Event; Functional disorder; Gene Expression; Genetic; Gynecologic; Hand; Immune; Immune System Diseases; In Vitro; Individual; Infertility; Inherited; Macrophage; Mesothelium; Microfluidic Microchips; Microfluidics; Molecular; Organ; Ovarian hormone; Ovary; Pain; Pathogenesis; Pathologic; Peripheral Blood Mononuclear Cell; Phenotype; Physiological; Polycystic Ovary Syndrome; Population; Property; Protocols documentation; Research; Research Personnel; Resources; Retrograde Menstruation; Stromal Cells; System; Technology; Time; Tissues; Uterus; Variant; Woman; aged; cell bank; chronic pelvic pain; differentiation protocol; endometrial organoid; endometriosis; experience; genetic variant; genome wide association study; girls; induced pluripotent stem cell; innovative technologies; insight; microfluidic technology; microphysiology system; monocyte; novel; novel strategies; reproductive; technology platform; tissue/cell culture; tool; transcriptome sequencing

ABSTRACT Endometriosis affects an estimated 176 million women and girls of reproductive age, worldwide, causing chronic pelvic pain and infertility. Despite the fact that most women experience retrograde menstruation, only 10% of women present with this condition, the underlying reasons for which are still unclear. The primary objective of this project is to explore the genetic basis for endometriosis pathophysiology through the application of innovative technologies and model systems. We have successfully produced induced pluripotent stem cells (iPSC) derived from blood cells of women with endometriosis and developed a novel microfluidic device capable of co-culturing cells and tissues. In this study, we aim to differentiate iPSCs into endometrial epithelial and stromal cells, as well as macrophages, and compare their behavior to that of cells derived from women without the condition. By using the microfluidic device, we will construct an endometriosis-immune chip that will enable us to investigate the interaction of endometrial cells with macrophages from endometriosis. Furthermore, we will conduct a comprehensive analysis of DNA variants in the iPSC lines and correlate them with gene expression and cell function, providing a comprehensive, unbiased, and global perspective of inherent differences in endometriosis cells. These cutting-edge technologies will allow us to explore previously unexplored areas of research, offering significant insights into endometriosis and advancing the field of endometriosis research considerably.

摘要 据估计，全世界有1.76亿育龄妇女和女孩患有子宫内膜异位症，导致慢性 盆腔疼痛和不孕不育。尽管大多数女性经历了逆行月经，但只有10%的女性 女性目前患有这种情况，其潜在原因仍不清楚。的主要目标是 本项目旨在通过应用创新的方法探索子宫内膜异位症病理生理学的遗传学基础 技术和模型系统。我们已经成功地培养出了诱导多能干细胞(IPSC) 从子宫内膜异位症患者的血细胞中提取并开发了一种新型的可共培养的微流体装置 细胞和组织。在本研究中，我们的目标是将ipscs分化为子宫内膜上皮细胞和间质细胞。 作为巨噬细胞，并将它们的行为与来自没有这种情况的妇女的细胞的行为进行比较。通过使用 微流控装置，我们将构建一个子宫内膜异位症免疫芯片，使我们能够研究 子宫内膜异位症患者子宫内膜细胞与巨噬细胞的相互作用。此外，我们将进行一项 IPSC系DNA变异的综合分析及其与基因表达和细胞的相关性 功能，为子宫内膜异位症的内在差异提供了一个全面、公正和全球的视角 细胞。这些尖端技术将使我们能够探索以前未探索的研究领域，提供 对子宫内膜异位症的重大见解，极大地推进了子宫内膜异位症的研究领域。