{"paper_id":"0d2e751b-3336-4c62-90dd-94f94dbc7b97","body_text":"ABSTRACT\nIntroduction\nThe human endometrium is a highly regenerative tissue that contains mesenchymal stem/stromal cells (MSCs). These MSCs are sourced via office-based biopsies and menstrual fluid, providing a less invasive and readily available option for cell-based therapies. This review provides an update on endometrial-derived MSCs as a treatment option for gynecological diseases.\nAreas covered\nThis narrative review covers the characterization and therapeutic mechanisms of endometrium biopsy-derived MSCs (eMSCs) and menstrual fluid-derived mesenchymal stromal cells (MenSCs), highlighting similarities and differences. It also covers studies of their application in preclinical animal models and in clinical trials as potential cell-based therapies for gynecological diseases.\nExpert opinion\neMSCs and MenSCs from a homologous tissue source have the potential to promote regenerative activity as a treatment for gynecological diseases. Both eMSCs and MenSCs demonstrate therapeutic benefits through their paracrine activity in tissue regeneration, immunomodulation, angiogenesis, and mitigating fibrosis. Further research is essential to establish standardized isolation and characterization protocols, particularly for heterogeneous MenSCs, and to fully understand their mechanisms of action. Implementing SUSD2 magnetic bead sorting for purifying eMSCs from endometrial tissues and menstrual fluid is crucial for their use in future cell-based therapies. Optimization of production, storage, and delivery methods will maximize their therapeutic effectiveness.\nArticle highlights\nMSC can be obtained from human endometrium non-invasively from endometrial biopsies and menstrual fluid, a source that regenerates monthly, allowing multiple collections from the same donor.\nA single surface marker, SUSD2, provides a simple isolation protocol for purifying mesenchymal stem cells (MSCs), including endometrial MSCs (eMSCs), using magnetic bead sorting, which preserves cell viability and yields perivascular MSCs. This approach is preferable for clinical applications compared to complex, fluorescence-activated cell sorting (FACS) using multiple markers and requires expensive equipment (flow cytometer).\nMenSCs, cultured directly from menstrual fluid similar to BM-MSC, are heterogeneous and donor-dependent, leading to variability in potency that can yield unexpected therapeutic results. The isolation protocol for enriching MSCs from menstrual fluids needs refinement for better therapeutic efficacy.\nThe therapeutic potential of eMSCs and MenSCs has been shown in various gynecological disease models: intrauterine adhesions (IUA), Asherman’s syndrome, and thin unresponsive endometrium by stimulating endometrial regeneration and improving endometrial function, and in pelvic organ prolapse by immunomodulation of the foreign body response to implanted meshes.\nSmall extracellular vesicles (sEVs) from eMSCs and MenSCs are promising off-the-shelf therapeutic agents due to their stability, low immunogenicity, and ability to target specific cells, influencing inflammation and tissue repair.\nTo date, no clinical study has utilized SUSD2+ eMSCs, while MenSCs have been investigated in several clinical trials for the treatment of diseases such as COVID-19 and primary ovarian insufficiency.\nThe therapeutic properties and clinical effectivities of MenSCs can be further improved by optimizing isolation protocols, culture conditions, and delivery methods. Both eMSCs and MenSCs could improve outcomes by utilizing the latest technologies such as genetic manipulation.\nDeclaration of interest\nThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.\nReviewer disclosures\nPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.\nAuthor contributions\nA Sadiasa: literature search, designing – tables and figures, writing – original draft, review, and editing. JA Werkmeister: supervision and Writing – review and editing. S Gurung: conceptualization, supervision, and writing – review and editing. CE Gargett: funding acquisition, conceptualization, supervision, and writing – review and editing. All authors contributed to the article and approved the submitted version.\nAcknowledgments\nThe graphical abstract was created in BioRender. Sadiasa, A. (2025) https://BioRender.com/k04z500.","source_license":"CC0","license_restricted":false}