Unlocking the Secrets of the Endometrium: Stem Cells, Niches and Modern Methodologies

The endometrium is a highly dynamic tissue central to female reproductive function, undergoing nearly 500 cycles of proliferation, differentiation, shedding, and regeneration throughout a woman's reproductive life. This remarkable regenerative capacity is driven by a reservoir of endometrial stem/progenitor cells (ESCs), which are crucial for maintaining tissue homeostasis. Dysregulation of these cells is linked to a variety of clinical disorders, including menstrual abnormalities, infertility, recurrent pregnancy loss, and serious gynecological conditions such as endometriosis and endometrial cancer. Recent advancements in organoid technology and lineage-tracing models have provided insights into the complex cellular hierarchy that underlies endometrial regeneration and differentiation. This review highlights the latest breakthroughs in endometrial stem cell biology, focusing particularly on 3D in vitro platforms that replicate endometrial physiology and disease states. By integrating these cutting-edge approaches, we aim to offer new perspectives on the pathogenesis of endometrial disorders and establish a comprehensive framework for developing precision regenerative therapies.