Intraglandular injection of amniotic-derived stem cell metabolites enhances submandibular gland regeneration in diabetic male rats.

This study investigates the potential regenerative capabilities of intraglandular injections of Amniotic-derived Mesenchymal Stem Cell Metabolite Products (AMSC-MP) on the structure and function of the submandibular glands in diabetic rat models. Forty male Wistar rats (±250 g, 2-3 months old) were induced to diabetes via intraperitoneal alloxan monohydrate injection (90 mg/kg BW). Following confirmation of diabetes (72 h post-injection), animals were randomised into a vehicle-treated diabetic control group and a treatment group (100 µL AMSC-MP), which were both further divided based on observation time points (day 3, 5, 7, and 10; n = 5). Daily intraglandular injections were administered, and glands were harvested at each respective time point for immunohistochemical analysis of SRY-box Transcription Factor 2 (SOX2), CD44, Ki67, Stromal Cell-Derived Factor 1 (SDF1), Vascular Endothelial Growth Factor (VEGF), and Mucin 5B (MUC5B). Immunohistochemistry demonstrated that AMSC-MP treatment reactivated the glandular regenerative niche. Quantitative analysis revealed a distinct temporal cascade: progenitor expansion (SOX2, CD44) and chemotactic signalling (SDF1) were significantly upregulated as early as day 3, whereas angiogenesis (VEGF) became prominent from day 5 onwards, culminating in active epithelial proliferation (Ki67) and secretory function recovery (MUC5B) by day 10 (p < 0.05). Intraglandular injection of AMSC-MP reactivated endogenous progenitor cells, promoted epithelial proliferation, and restored glandular function in diabetic rats. These findings highlight the therapeutic potential of AMSC-derived metabolites as an acellular regenerative approach for diabetic salivary gland regeneration.