The evolution of endometriosis research models: a paradigm shift from immortalized cell lines to organoids†

Endometriosis is a complex condition affecting 10% of reproductive-age women worldwide, yet its study has long been hindered by the shortcomings of traditional research models. This review aims to propose a novel theoretical framework and strategic roadmap to accelerate precision medicine in endometriosis. We systematically trace the evolution of research models in the field and critically assess the inherent constraints of conventional systems, including immortalized cell lines and primary cell cultures. While immortalized lines often fail to capture patient heterogeneity due to genetic drift, animal models cannot fully replicate the human immune microenvironment. Although primary cells preserve patient-specific traits and support personalized drug testing, their two-dimensional culture format limits their ability to mimic the three-dimensional (3D) architecture and dynamic cell-cell interactions of native tissues. Recent breakthroughs in organoid technology are reshaping endometriosis research by enabling 3D structural reconstruction, hormone responsiveness, and simulation of lesion progression. This review highlights the transformative potential of organoids in disease modeling, drug screening, and personalized therapy. We also discuss future opportunities for integrating organoids with emerging platforms-such as organ-on-a-chip systems, multi-omics analyses, and digital twin technology-to open new avenues for understanding disease mechanisms and advancing targeted treatments.