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

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.

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.

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).

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. Similar content being viewed by others Data availability The datasets obtained during the present review are available from the corresponding author upon reasonable request. Abbreviations - ADSCs: - Adipose-derived stem cells - BMMSCs: - Bone marrow mesenchymal stem cells - COX-2: - Cyclooxygenase-2 - ELISA: - Enzyme-linked Immunosorbent Assay - eMSCs: - Endometrial mesenchymal stem cells - ERβ: - Oestrogen receptor beta - GnRH: - Gonadotrophin-releasing hormone - HUVEC: - Human umbilical vein endothelial cells - IF: - Immunofluorescence - IHC: - Immunohistochemistry - MenSCs: - Menstrual blood-derived mesenchymal stem cells - MMPs : - Metalloproteinases - NO: - Nitric oxide - N.S.: - Number of studies - NSAIDs: - Non-steroidal anti-inflammatory drugs - PCR: - Polymerase Chain Reaction - PRISMA: - Preferred Reporting Items for Systematic Reviews and Meta-Analyses - TAC: - Total antioxidant capacity - TUNEL: - Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling - UCMSCs: - Umbilical cord mesenchymal stem cells - WB: - Western blotting - WJSCs: - Wharton's jelly stem cells

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The authors would like to sincerely thank Nuria González for her invaluable assistance in the design, preparation, and improvement of the figures included in this manuscript. Funding This research was funded by: Plan Complementario de Biotecnología Aplicada a la Salud, co-financed by the Ministry of Science and Innovation with funds from the European Union's NextGenerationEU initiative; by Instituto de Salud Carlos III (ISCIII) through RICORS/TERAV (RD21/0017/0014) supported by European Union's NextGenerationEU and Recovery, Transformation and Resilience Plan, by Consejería de Educación, Ciencia y Formación Profesional of the Junta de Extremadura (GR24210), co-funded by the European Regional Development Fund (ERDF) and with support to I. Suárez-Carrasco from MAFRESA, EL IBÉRICO DE CONFIANZA SL. Author information Authors and Affiliations Contributions I. Suárez-Carrasco and E. López: conceptualisation, methodology, literature search, data extraction and formal analysis. M.A. De Pedro, M. Pulido and V. Álvarez: writing (review and editing). F.M. Sánchez-Margallo: supervision, project administration and funding acquisition. All authors read and approved the final version of the manuscript. Corresponding author Ethics declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. About this article Cite this article Suárez-Carrasco, I., De Pedro, M., Pulido, M. et al. Stem cell therapy-based approaches in experimental endometriosis: a systematic review. Reprod Biol Endocrinol (2026). https://doi.org/10.1186/s12958-026-01553-w Received: Accepted: Published: DOI: https://doi.org/10.1186/s12958-026-01553-w