Dental pulp-derived mesenchymal stem cells reduce lesion progression in a rat model of endometriosis

Endometriosis is a chronic, estrogen-dependent inflammatory disease sustained by aberrant angiogenesis and progressive fibrosis. We evaluated the therapeutic efficacy of human dental pulp-derived mesenchymal stem cells (DP-MSCs) in a surgically induced rat endometriosis model. Twenty-eight adult female Wistar rats were randomized (n = 7/group) to sham group (G1), untreated endometriosis-group (G2), single-dose DP-MSCs-group (G3) (2 × 10⁶ cells intraperitoneally on day 28) and double-dose DP-MSCs-group (G4) (2 × 10⁶ cells on days 28 and 35). Endometriosis was induced by autologous uterine tissue implantation onto the peritoneal wall and allowed to establish for 28 days; treatment effects were assessed 7 days after the final DP-MSCs dose. Serum and peritoneal TNF-α, IL-6, VEGF, and CA-125 were quantified; lesions were evaluated by semi-quantitative histopathology and fibrosis grading and by immunohistochemistry for CA-125, VEGF, type I collagen (Col1), and TNF-α. Untreated endometriosis showed increased systemic TNF-α (p = 0.0207) and IL-6 (p = 0.0003) and marked peritoneal elevations versus sham (all p < 0.0001). DP-MSCs treatment significantly reduced peritoneal TNF-α and IL-6 in both regimens (each p < 0.0001 vs untreated) and decreased peritoneal VEGF, with greater suppression after double dosing (p = 0.0100 between regimens). Double dosing produced stronger systemic TNF-α suppression (p = 0.0027 vs untreated). Histopathology and fibrosis improved, most prominently with double dosing (both p < 0.0001), accompanied by reduced CA-125, VEGF, Col1 and TNF-α immunoreactivity (CA-125 and TNF-α, p < 0.0001). DP-MSCs effectively resolve the hallmark pathological features of endometriosis in a dose-dependent manner. By synergistically targeting inflammatory, angiogenic, and fibrotic pathways, this cell-based strategy offers a potent, disease-modifying approach for clinical management.