Microphysiological modeling of Endometriosis

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.