A Novel Strategy Using Dental Pulp Stem Cells and Jiarong Tablets to Treat Intrauterine Adhesions in Rats

ABSTRACT Aim To evaluate the efficacy and underlying mechanisms of dental pulp stem cells (DPSCs), alone or with Jiarong Tablets, for the treatment of intrauterine adhesions (IUAs) in rats. Methods IUAs were induced in Sprague Dawley (SD) rats. The rats were randomly assigned to the following groups ( n = 18/group): Sham, IUA, IUA + Estrogen, IUA + low−/medium−/high‐dose DPSC (5 × 10 5 , 1 × 10 6 and 2 × 10 6 cells), IUA + DPSC + Estrogen (1 × 10 6 DPSCs + estradiol (E2)), and IUA + DPSC + Jiarong Tablets (1 × 10 6 DPSCs +40 mg/mL Jiarong Tablet administered by gavage). At 28 days post‐establishment, the rats were sacrificed ( n = 12/group) and assessed for endometrial morphology, gland count, fibrosis, serum E2 levels, and PKH26‐labeled DPSC tracking, and protein and mRNA analyses of connective tissue growth factor (CTGF), estrogen receptor alpha 1 (ESR1), transforming growth factor beta 1 (TGF‐β1), and vascular endothelial growth factor (VEGF) were conducted. Fertility was evaluated on gestational Day 14 after mating ( n = 6/group). Results Compared with the rats in the sham group, the rats in the IUA group exhibited uterine occlusion, a reduced number of endometrial glands, increased fibrosis, decreased serum E2 levels ( p < 0.01), and more irregularly shaped glands ( p < 0.05). Treatment with DPSCs (all doses) and combination therapies significantly improved uterine morphology and reduced fibrosis and E2 levels ( p < 0.05). Treatment with low‐ and medium‐dose DPSCs increased gland count ( p < 0.05), whereas treatment with DPSCs + Jiarong Tablet reduced the number of irregularly shaped glands ( p < 0.01). The fluorescence intensity of DPSCs was dose‐dependent in uterine and ovarian tissues ( p < 0.05). The occurrence of IUAs significantly increased the expressions of CTGF, TGF‐β1, and VEGF, which were reversed following treatment ( p < 0.05). ESR1 expression was significantly increased after treatment with DPSC and Jiarong Tablet ( p < 0.05). Fertility outcomes improved significantly in all treatment groups. Conclusions DPSCs were used to effectively treat IUAs, with 1 × 10 6 cells being identified as the optimal dose. Combining DPSCs with Jiarong Tablets further enhanced the therapeutic outcomes by modulating the levels of fibrosis‐related factors (CTGF, TGF‐β1) and angiogenesis factor (VEGF) and estrogen response (ESR1).