Effectiveness of BMMSC and Dienogest on IL-1β, IL-8 Expression and Lesion Area in Endometriosis Mice.

Abstract

Objective: Endometriosis is a chronic estrogen-dependent inflammatory disease that impairs fertility and quality of life. Dienogest, the current standard therapy, provides symptom relief but does not correct immune imbalance or prevent recurrence. Bone marrow-derived mesenchymal stem cells (BMMSCs), with strong immunomodulatory potential, may represent a disease-modifying alternative. This study evaluated the effects of BMMSCs, Dienogest, and their combination on IL-1β and IL-8 expression and lesion size in a murine endometriosis model.

Methods: The experiment was conducted between August and December 2024 using 32 female mice, randomly assigned into four groups: untreated endometriosis controls (K+), BMMSC monotherapy (P1), BMMSC combined with Dienogest (P2), and Dienogest monotherapy (P3). Mice were injected intraperitoneally with endometrial fragments (200 μL) to become endometriosis models. On day 15, the models received mesenchymal stem cells. Sample collection was on day 29. Cytokine expression (IL-1β and IL-8) was assessed immunohistochemically, while lesion dimensions were analyzed using ImageJ v1.54 (NIH, USA) software. Immunofluorescence confirmed the BMMSC phenotype (CD73+, CD90+, CD105+, CD45-). Statistical analysis used one-way ANOVA and Kruskal-Wallis with Bonferroni correction.

Results: BMMSC monotherapy resulted in the most pronounced suppression of IL-1β and IL-8 expression, alongside a significant reduction in lesion size (p<0.001). All treatment groups differed significantly from the control group.

Conclusions: BMMSC monotherapy in endometriosis mice models markedly reduced IL-1β and IL-8 expression, decreased lesion size, and demonstrated more robust disease-modifying activity compared to Dienogest or combination therapy.