Targeting endometrial stem cell in endometriosis treatment, a scoping review

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.

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.

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.

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.