MEN-ENDO: Menstrual Stem Cells in Endometriosis

NCT07578480 | Recruiting

• 1 other identifier: MEN-ENDO CEIm 308/2025
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

Endometriosis is a chronic inflammatory condition characterized by the presence of endometrium-like tissue outside the uterine cavity. It is estimated to affect approximately 10% of women of reproductive age and it is associated with chronic pelvic pain and infertility, among other symptoms. Endometriosis involves complex changes in the body's cells and immune response. For this reason, the goal of this observational study is to characterize the functional, molecular, and immunological alterations in menstrual blood-derived stem cells (MenSCs) and differentiated decidual stromal cells in women with endometriosis; to validate these findings in endometrial tissue and endometriomas; and to establish their correlation with clinical parameters, with the aim of identifying key pathogenic mechanisms and potential therapeutic targets. The main questions it aims to answer are:

• Are there functional and molecular changes in MenSCs from patients with endometriosis compared to healthy volunteers?
• Are there any variations in the immune properties of MenSCs throughout the menstrual bleeding period in patients with endometriosis compared to healthy volunteers?
• Are these changes also present in endometrial tissue and endometrioma samples?
• Can these changes be correlated with clinical parameters in patients with endometriosis?
• Can MenSCs serve as a potential therapeutic target for endometriosis? Some participants will be asked to provide menstrual blood on a single day, while others will provide samples during the first five days of menstruation. Additionally, all participants will answer questionnaires about their diet, physical activity, stress, and pain levels. Therefore, the study does not involve the evaluation of a specific intervention on the participants. The results will enable the identification of key altered mechanisms and potential therapeutic targets, thereby contributing to the development of more effective strategies for the diagnosis and treatment of the disease.

Conditions

Endometriosis

Keywords

Menstrual blood-derived stem cells; Menstrual blood

Outcome Measures

Primary Outcomes (26)

• MenSCs proliferation rate

  Evaluation of the expansion capacity of MenSCs from endometriosis patients vs. healthy controls using the MTT assay.

  Through study completion (average of 3 years)

• Phenotypic characterization of MenSCs

  Evaluation of surface marker expression using flow cytometry to determine the phenotype of MenSCs from endometriosis patients and healthy controls.

  Through study completion (average of 3 years).

• MenSC chemotaxis

  Assessment of the number of T-lymphocytes and monocytes capable of migrating through a transwell membrane under the stimuli of conditioned media from MenSCs obtained from endometriosis patients and healthy controls.

  Through study completion (average of 3 years)

• MenSC invasion capacity

  Assessment of the number of MenSCs from endometriosis patients vs. healthy controls capable of degrading a Matrigel on a transwell membrane and migrating toward a chemoattractant.

  Through study completion (average of 3 years)

• Multilineage capacity of MenSCs

  The differentiation potential of MenSCs from endometriosis patients vs. healthy controls towards osteocytes, chondrocytes and adipocytes will be assessed by using specific media.

  Through study completion (average of 3 years)

• Decidualitzation response to progesterone of the decidual cells differentiated from MenSCs from endometriosis patients and healthy volunteers

  MenSCs will be cultured in presence of 8-Br-cAMP during 14 days, and the assessment of morphology and expression of decidual markers will be performed by RT-qPCR and ELISA assay.

  Through study completion (average of 3 years).

• Apoptosis resistance assessment of the decidual cells differentiated from MenSCs from endometriosis patients and healthy volunteers

  Apoptosis resistance will be evaluated by Annexin V/PI flow cytometry following induction by TNFα. Additionally, the expression of key apoptotic mediators will be quantified using RT-qPCR and Western blot.

  Through study completion (average of 3 years).

• Cytokine profile of the secretome of MenSCs from endometriosis patients and healthy volunteers and their differentiated decidual cells.

  The conditioned media will be assessed to determine the cytokines secreted using an ELISA assay.

  Through study completion (average of 3 years).

• Cytokine profile of the endometrial and endometrioma tissues

  The levels of cytokines in the conditioned media from cultured explants will be assessed by ELISA assay.

  Through study completion (average of 3 years).

• Cytokine profile of the secretome of immune cells populations

  The levels of cytokines in the conditioned media from lymphocytes and macrophages will be assessed by ELISA assay.

  Through study completion (average of 3 years)

• Cytokine profile of the peripheral blood plasma

  The levels of cytokines in peripheral blood plasma from endometriosis patients and healthy volunteers will be determined by ELISA assay.

  Through study completion (average of 3 years)

• Gene expression profile of MenSCs from endometriosis patients and healthy volunteers and their differentiated decidual cells

  Total RNA expression of targeted genes will be analyzed by RT-qPCR.

  Through study completion (average of 3 years)

• Gene expression profile of the endometrial and endometrioma tissues

  Total RNA expression of targeted genes will be analyzed by RT-qPCR.

  Through study completion (average of 3 years).

• Gene expression profile of the immune cells populations

  Total RNA expression of targeted genes will be analyzed by RT-qPCR.

  Through study completion (average of 3 years)

• Protein expression of MenSCs from endometriosis patients and healthy volunteers and their differentiated decidual cells

  Analysis of the protein expression profile via Western Blot.

  Through study completion (average of 3 years)

• Protein expression in endometrial and endometrioma tissues

  Analysis of the protein expression profile via Western Blot.

  Through study completion (average of 3 years)

• Protein expression in immune cells populations

  Analysis of the protein expression profile via Western Blot.

  Through study completion (average of 3 years)

• T cells activation

  T cells will be exposed to conditioned media from MenSCs from healthy volunteers and endometriosis patients. Afterwards, the levels of IL-10 and IFNy will be determined by ELISA assay.

  Through study completion (average of 3 years)

• T cells proliferation rate

  T cells will be exposed to conditioned media from MenSCs from healthy volunteers and endometriosis patients. Afterwards, their proliferative capacity will be assessed by MTT assay.

  Through study completion (average of 3 years)

• Cytokine secretion profile of macrophages

  The levels of cytokines in the supernatant of polarized macrophages after incubation with MenSC-derived conditioned media from endometriosis patients and healthy volunteers will be determined by ELISA assay.

  Through study completion (average of 3 years)

• Gene expression profile of macrophages

  Total RNA expression of targeted genes will be analyzed by RT-qPCR.

  Through study completion (average of 3 years)

• Protein expression of macrophages

  Analysis of the protein expression profile via Western Blot.

  Through study completion (average of 3 years)

• Phagocytic capacity of macrophages

  Assessment of the macrophages' ability to engulf fluorescently labeled apoptotic bodies from MenSCs via flux cytometry and fluorescence microscopy.

  Through study completion (average of 3 years)

• Angiogenic potential of macrophages conditioned media

  Evaluation of the ability of macrophage-derived conditioned media to induce tube formation (Matrigel) in Human Umbilical Vein Endothelial Cells (HUVECs).

  Through study completion (average of 3 years)

• Exploration of targeted interventions to reverse the pathological phenotype of MenSCs and macrophages derived from menstrual blood.

  Signaling pathways and genes involved in the altered phenotype will be blocked and silenced, respectively, to evaluate if these actions reverse the cellular response to the levels of the healthy volunteers' cells.

  Through study completion (average of 3 years).

• Correlation of cellular, tissue and molecular findings with patients' clinical parameters.

  The associations among the functional and immunological properties of MenSCs and macrophages, clinical parameters and dietary and behavioral habits will be stablished. These clinical parameters include endometriosis stage, pain and fertility status, and the extent and localization of the endometriosis foci.

  Through study completion (average of 3 years).

Study Arms (1)

Endometriosis

Other: Menstrual blood-derived stem cells collection and in vitro characterization

Interventions

Menstrual blood-derived stem cells collection and in vitro characterization OTHER

Menstrual-blood derived stem cells will be isolated from the menstrual blood of patients with endometriosis and healthy volunteers to be characterized in vitro.

Endometriosis

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Our study population consists of 40 women aged between 18 and 45, 20 of whom have been diagnosed with endometriosis and 20 of whom are healthy volunteers. Participants will be recruited from the Department of Gynecology and Obstetrics at the Hospital Universitari Joan XXIII in Tarragona (Spain) during routine gynecological check-ups. Healthy volunteers will be selected through individual matching with participants in the study group, considering relevant demographic and clinical variables such as age and ethnic group. In addition, a sub-cohort of 10 women (5 per study group) will be selected from the main cohort to study in greater detail the intra-menstrual variations in the immunomodulatory properties of MenSCs. This sub-cohort will include participants who agree to provide menstrual blood samples from days 1 to 5 (both inclusive) to analyze dynamic changes in the cells obtained, while maintaining the same general inclusion and exclusion criteria as in the main study.

You may qualify if:

• years.
• Endometriosis group: Women with clinical and/or ecographical diagnostic of endometriosis.
• Control group: Women with the endometriosis diagnosis.

You may not qualify if:

• \<18 years or \>45 years.
• Pregnancy or lactation.
• Diagnosis of prior chronic pelvic inflammatory or autoimmune disease.
• History of active gynecological cancer.
• Positive for human immunodeficiency virus (HIV) or human papillomavirus (HPV).
• Hormonal therapy use in the previous 3 months.
• Use of immunosuppressants or corticosteroids in the previous 3 months.
• Systemic antibiotics use in the previous 3 months.
• Insufficient menstrual flow to allow the MenSCs isolation.

Sponsors & Collaborators

• Francisco Algaba Chueca: lead
• Hospital Universitari Joan XXIII de Tarragona.: collaborator

Study Sites (2)

Universitat Rovira i Virgili. Facultat de Medicina i Ciències de la Salut

Reus, Tarragona, 43201, Spain

ACTIVE NOT RECRUITING

Hospital Universitari Joan XXIII

Tarragona, Tarragona, 43005, Spain

RECRUITING

MeSH Terms

Conditions

Endometriosis

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Central Study Contacts

Dr. Francisco Algaba-Chueca

CONTACT

+34623966066; francisco.algaba@urv.cat

Dr. Victoria Linares-Vidal

CONTACT

+34977759374; mvictoria.linares@urv.cat

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior Lecturer

Study Record Dates

• First Submitted: April 13, 2026
• First Posted: May 11, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: May 11, 2026

Record last verified: 2026-05

Locations

ES (2)