Stem cell therapy-based approaches in experimental endometriosis: a systematic review

Abstract Background Stem cell-based therapies have emerged as a promising approach for endometriosis due to their regenerative and immunomodulatory properties. Although numerous preclinical studies have reported beneficial effects, no systematic synthesis has yet evaluated their impact, the models employed and associated biomarkers. Therefore, the aim of this systematic review is to synthesise all available preclinical evidence (both in vitro and in vivo) assessing stem cell-based therapies and stem cell-derived products in experimental models of endometriosis. Methods Following PRISMA guidelines, PubMed, Scopus and Web of Science were searched from 1 January 2015 up to 11 February 2025. Preclinical studies (in vitro and in vivo) evaluating stem cell-based therapies in experimental models of endometriosis were included. Data were extracted regarding the models employed, cell sources, analysed biomarkers and reported cellular outcomes. Results Twenty preclinical studies were included, employing a wide range of in vitro models (most commonly endometriotic cells) and predominantly murine in vivo models induced by intraperitoneal injection of uterine tissue. Adipose-derived stem cells (ADSCs) and bone marrow-mesenchymal stem cells (BMMSCs) were the most frequently investigated cell sources. Across the studies, VEGFA, TNFA, metalloproteinases (MMPs) and components of the PI3K/AKT/mTOR pathway were the most consistently analysed biomarkers, primarily assessed by PCR and immunohistochemistry. Overall, 72 of the 92 reported outcomes were positive, with ADSCs demonstrating the most pronounced therapeutic effects and being characterised by their immunomodulatory, anti-inflammatory and regenerative activity. Negative or neutral findings, such as increased cellular adhesion and invasion, were limited and largely associated with ADSCs and umbilical cord mesenchymal stem cells (UCMSCs). Conclusions Stem cell-based therapies demonstrate promising effects in experimental endometriosis, with most studies reporting improvements in lesion characteristics and inflammatory pathways. However, substantial variability in models, cell types and outcomes limits the strength of current evidence. More standardised and rigorous preclinical research is needed to confirm these findings and support the translation of stem cell therapy-based approaches into future clinical practice.