New iPSC Platform Offers a Human Model for Studying Endometriosis

A stem cell–based platform derived directly from patients with endometriosis can model key molecular and hormonal features of the disease in a controlled human context, giving researchers a new way to study its biology, according to a study published in Science Advances.¹

A Model Built Around Old Limitations

Endometriosis affects an estimated 10% of women of reproductive age worldwide, or roughly 190 million people, and diagnosis is often delayed by 4 to 12 years, according to the WHO.² The chronic disease occurs when tissue similar to the lining of the uterus grows outside it, driving pelvic pain, heavy bleeding, and infertility; there is currently no cure.

Despite that burden, research using human endometrial stromal cells has long been constrained by limited tissue availability, variability in donor menstrual cycle stage, and the short lifespan of stromal cells in culture.¹ To work around those constraints, the researchers developed a platform using induced pluripotent stem cells (iPSCs) derived from patients with endometriosis. Because iPSCs retain a patient's genetic background, the model can incorporate inherited risk factors tied to the disease's well-established heritable component, something prior systems could not do.

“To provide biological context for these in vitro–derived cell states, we benchmarked their transcriptional profiles against an independent human stromal reference dataset generated from endometriosis patient tissues,” wrote the researchers of the study. “This integrative approach enabled assessment of transcriptional convergence toward stromal programs.”

Gene Expression Overlapped With Published Disease Data

Using a defined differentiation protocol, the researchers guided endometriosis-derived iPSCs through pluripotency and mesenchymal commitment toward stromal-like cells that acquired hormone responsiveness. To validate the platform, they compared gene expression in these iPSC-derived endometrial stromal fibroblasts with previously published gene expression data from adult endometrial stromal cells of patients with endometriosis and found a significant number of overlapping disease-associated pathways.

The iPSC-derived cells did diverge from adult cells in one respect: their epigenetic pathways looked distinctly different. The researchers noted that this gap may itself be meaningful: because epigenetic changes are shaped by environmental cues such as chronic inflammation, she said the findings suggest endometriosis reflects persistent inflammatory signaling that reprograms gene regulation, not just genetic susceptibility.

Stromal Secretions Reprogrammed Immune Cells in the Lab

The researchers also tested whether the iPSC-derived stromal cells could influence immune cells. Conditioned media, the nutrient fluid left behind after cells are cultured in it, collected from the endometriosis-derived stromal cultures, was applied to THP-1 cells, a standard macrophage-like cell line, and triggered substantial transcriptional reprogramming there. The shifted pathways included interleukin-2/STAT5 signaling, TGF-β signaling, and epithelial-mesenchymal transition, all of which are tied to immune activation and tissue remodeling. The authors wrote that this points to altered stromal-immune crosstalk as a possible shared feature of endometriosis and related uterine conditions such as adenomyosis and offers proof of concept that the platform can be used to functionally probe immune modulation, not just hormonal or structural changes.

The authors cautioned that the study's cohort size and design limit its ability to draw firm conclusions about disease-specific differences but described the framework as a scalable, genetically defined system for future research incorporating larger cohorts, targeted genetic perturbations, and therapeutic screening.

“Beyond the specific findings reported here, iPSC-based models offer several unique advantages for studying endometriosis,” wrote the researchers. “iPSCs provide a renewable, patient-specific resource that can be differentiated into multiple relevant cell types from the same genetic background, enabling systematic studies of cell-cell interactions and tissue cross-talk. iPSCs are also amenable to genetic manipulation, including targeted perturbation of candidate genes or pathways, and to scalable drug or perturbation screens. Together, these features position iPSC-derived systems as a powerful experimental bridge between human genetics, cell biology, and translational therapeutic discovery.”

References

1. McDowell H, Sun S, McNally R, et al. Endometriosis-derived iPSCs reveal conserved stromal maturation and endocrine responsiveness. Science Advances. 2026;12(34). doi:10.1126/sciadv.aeg2362
2. Endometriosis. World Health Organization. Updated October 15, 2025. Accessed September 10, 2026. https://www.science.org/doi/10.1126/sciadv.aeg2362