Introduction Endometriosis is characterized by the ectopic implantation of endometrial tissue affecting reproductive-aged women. Available therapies have still unmet needs namely due to recurrence rates and systemic side effects. Emerging evidence suggests endometrial stem cells (EnSCs) contribution in disease pathogenesis, including mesenchymal stem cells (E-MSCs), epithelial progenitor cells (EPCs), and side population cells (ESPs). These stem/progenitor cells are involved in proliferation, migration, and angiogenesis, contributing to endometriosis genesis and persistence. Targeting EnSCs and their regulatory pathways present a promising therapeutic strategy to improve unmet needs in endometriosis. Materials and Methods This scoping review was based on a systematic literature search conducted in PubMed, EMBASE, and Web of Science considering studies published after 2000. Inclusion criteria focused on original research articles exploring the role and targeting of EnSCs in endometriosis, following PRISMA-ScR guidelines. Data were synthesized through narrative and descriptive methods. Results The review structures key pathways and therapeutic agents targeting EnSCs in endometriosis. Notch1, PI3K/Akt, Wnt/β-catenin, and JAK/STAT signalling are pathways that regulate proliferation, migration and survival of EnSCs in endometriosis. Agents such as metformin, lovastatin, sorafenib, quinagolide, and γ-secretase inhibitors demonstrated potential to modulate stemness, leading to a decrease in inflammation, migration and apoptosis. Anti-angiogenic agents showed efficacy in reducing lesion size in vivo, targeting E-MSCs. Exosomes emerge as a cell-free approach, derived from menstrual stem cells (MenSCs) or ginger-based nanoparticles and exhibited properties essential for endometriosis treatment, directed to ectopic stem cells. Conclusions EnSCs sustain aberrant cellular behaviours in endometriosis. Targeting EnSCs and their related pathways may be an innovative, individualized, and disease-modifying strategy. Pharmacological modulation, gene therapy and exosome are strategies for stem cell inhibition in endometriosis, being a promising avenue for future research leading to application in clinical practice.
Gonadotoxicity resulting from systemic and locoregional cancer treatments significantly threatens women’s reproductive health, often culminating in premature ovarian insufficiency. These therapies, particularly alkylating agents and ionizing radiation, induce DNA damage and apoptosis in ovarian follicles, leading to infertility, amenorrhea, and estrogen deficiency, which exacerbate risks of osteoporosis and cardiovascular diseases. Existing fertility preservation methods do not prevent immediate ovarian damage, underscoring the need for innovative protective strategies. Menstrual blood-derived stem cells (MenSC) and their extracellular vesicles (EV) present promising regenerative potential due to their therapeutic cargo delivery and pathway modulation capabilities. Preclinical studies demonstrate that MenSC-derived EV ameliorate premature ovarian insufficiency by inhibiting granulosa cell apoptosis, promoting angiogenesis, and activating pivotal pathways such as SMAD3/AKT/MDM2/P53. However, comprehensive research is imperative to ensure the safety, efficacy, and long-term effects of MenSC-derived EV in clinical practice. In this review, we update the current knowledge and research regarding the use of MenSC-derived EV as a novel therapeutic weapon for ovarian regeneration in the context of gonadotoxicity induced by systemic anticancer treatment.
Establishing an accurate prognosis for women diagnosed with breast cancer (BC) is extremely challenging. Axillary lymph node (ALN) evaluation is considered of major prognostic value. The one-step nucleic acid amplification (OSNA) assay is currently used for assessing axillary sentinel lymph node (SLN) status in BC. Additionally, total tumor load (TTL) may help predict further metastatic axillary involvement beyond the SLN. The prognostic value of primary BC location remains controversial due to lack of consensus on the biological differences among tumors at various sites. Evidence suggests that tumors in the internal quadrants (INLs) have worse prognosis compared to those in the external quadrants. Furthermore, ALN involvement is believed to be mainly associated with external quadrant tumors, mainly due to the lymphatic drainage system of the breast. This pilot observational study, despite lacking a control group and having a relatively small sample size, is the first to evaluate the potential relationship between primary BC location and ALN metastasis using the OSNA assay. A sample of consecutive BC patients undergoing axillary staging with the OSNA assay were included. Tumors were categorized into three groups based on primary location: external quadrants and axillary tail (EXL), INLs, and nipple and areola location (NAL). Although not statistically significant, the INL group exhibited a higher mean TTL. Additionally, no significant differences were observed between groups concerning SLN detection techniques, SLN status, number of metastatic SLN, or mean TTL. These findings support the use of the innovative tracer superparamagnetic iron oxide regardless of tumor site. This study underscores the importance of understanding the relationship between BC location and ALN status, which may improve prognostic stratification and targeted therapies based on tumor site. If these observations are confirmed in larger, multicentric studies, the potential conclusions may shift the paradigm of INL tumor treatment, significantly impacting clinical practice and research.
Risk-reducing bilateral salpingo-oophorectomy (RRSO) is recommended for breast cancer gene 1 (BRCA1) and 2 (BRCA2) mutation carriers. A major consequence of RRSO is surgical menopause associated with severe menopausal symptoms, mostly genitourinary complaints. Due to the inherent breast cancer risk, estrogen-based therapies are generally avoided in these patients. So far, the non-hormonal approaches available are not efficient to successfully treat the disabling vaginal atrophy-related symptoms. In regenerative medicine, mesenchymal stem cells (MSC) are the most frequently used cell type due to their remarkable and regenerative characteristics. Therapies based on MSC have revealed positive outcomes regarding symptoms and signs associated with vaginal atrophy by promoting angiogenesis, vaginal restoration, and the proliferation of vaginal mucosa cells. Menstrual blood-derived stem cells (MenSC) are a novel source of MSC, with promising therapeutic potential directly linked to their high proliferative rates; low immunogenicity; non-invasive, easy, and periodic acquisition; and almost no associated ethical issues. In this review, we update the current knowledge and research regarding the potential value of previously preserved MenSC in the therapy of vaginal atrophy among BRCA mutation carriers subjected to RRSO.
Objective: Abdominal wall endometriosis (AWE) is a rare form of extragenital endometriosis that usually develops in association with a prior surgical scar. The purpose of the study was to review the clinical characteristics, diagnostic methods, treatment modalities, and outcomes of patients with AWE. Methods: A descriptive cross-sectional study was performed in a Gynecology Department of a Portuguese tertiary hospital, concerning patients with histologic-proven AWE, between January 2012 and December 2020 (n = 22). Statistical analysis was performed using IBM SPSS Statistics Version 27.00, with a significance level of p < 0.05. Results: The most common locations of extrapelvic endometrial ectopic implants were cesarean delivery scar (n = 13, 59.1%) and the umbilicus (n = 5, 22.7%). The median (range) age was 36 (30-42) years old, and all patients had a history of previous surgery but one. Nineteen patients had undergone a previous cesarean section, and the mean (range) time from surgery to the onset of symptoms was 100 (32-168) months. All patients were symptomatic and presented with a palpable mass at physical examination. The majority complained of a painful abdominal mass (n = 20, 90.9%) which was associated with cyclic pain in thirteen patients (65%). Ultrasound scan was performed in all patients and the nodules had a median size of 20.5 mm (5-93 mm). One patient received hormonal therapy and surgical resection was performed in the remaining patients. The nodule’s median (range) size was 31 (12-50) mm on gross examination. Conclusion: AWE should be considered in the presence of a previous pelvic surgery history associated with abdominal scar cyclic pain and swelling. A careful history and clinical examination are essential for diagnosis to avoid unnecessary delay before surgical intervention.
The human endometrium has a complex cellular composition that is capable of promoting cyclic regeneration, where endometrial stem cells play a critical role. Menstrual blood-derived stem cells (MenSC) were first discovered in 2007 and described as exhibiting mesenchymal stem cell properties, setting them in the spotlight for endometriosis research. The stem cell theory for endometriosis pathogenesis, supported by the consensual mechanism of retrograde menstruation, highlights the recognized importance that MenSC have gained by potentially being directly related to the genesis, development and maintenance of ectopic endometriotic lesions. Meanwhile, the differences observed between MenSC in patients with endometriosis and in healthy women underlines the applicability of these cells as a putative biomarker for the early diagnosis of endometriosis, as well as for the development of targeted therapies. It is expected that in the near future MenSC will have the potential to change the way we manage this complex disease, once their long-term safety and effectiveness are assessed.
Ductal carcinoma in situ (DCIS) is a putative precursor of invasive breast cancer and MRI is considered the most sensitive imaging technique for its detection. This study aims to evaluate the accuracy of MRI measuring the pure DCIS size, against pathology, to better understand the role of MRI in the management of this intraductal neoplasm.Potentially eligible studies in MEDLINE, Embase and Google Scholar, up to January 2021 were considered, and a systematic review and meta-analysis according to the published protocol (Prospero-CRD42021232228) was performed. Outcomes of mean differences and accuracy rates were analysed using IBM® SPSS® v26 and random-effect models in platform R v3.3.Twenty-two cross-sectional studies were selected and 15 proceeded to meta-analysis. MRI accurately predicted 55% of the tumours’ sizes and, according to Bland–Altman plots, concordance between MRI and pathology was greater for smaller tumours. In the meta-analysis, difference of the means between MRI and pathology was 3.85 mm (CI 95% [−0.92;8.60]) with considerable heterogeneity (I2 = 96.7%). Subgroup analysis showed similar results for sizes between different MRI fields, temporal resolution, slice thickness and acquisition times, but lower heterogeneity in studies using 3-T MRI (I2 = 57.2%). Results were concordant with low risk of bias studies (2.46, CI 95% [0.57–4.36]), without heterogeneity (I2 = 0%).Therefore, MRI is shown to be an accurate method in pure DCIS size assessment. Once the best MRI protocol is established, evaluation of the impact of pure DCIS size in predicting treatment outcomes will contribute to clarifying current issues related to intraductal breast carcinoma.