Human umbilical cord-derived mesenchymal stem cells alleviate lesions of the submandibular gland via B cell modulation and inflammatory cytokine suppression

Background: Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) possess inherent exhibit immunomodulatory and anti-inflammatory properties, rendering them promising therapeutic candidates for treating autoimmune diseases. However, their therapeutic efficacy against submandibular gland lesions (SGL), such as those associated with Sjögren syndrome (SS), remains incompletely elucidated and warrants further investigation. This study aims to systematically evaluate the dose-dependent therapeutic efficacy of UC-MSCs in NOD/Ltj mice with spontaneous SGL and clarify the immunomodulatory mechanisms mediated by B cell regulation and inflammatory cytokine inhibition.

Methods: Female non-obese diabetic (NOD) mice (8 weeks old) with spontaneous SGL were intravenously administered UC-MSCs at three distinct doses (2.5×10⁵, 5×10⁵, and 1×10⁶ cells / mouse). Clinical parameters (body weight, blood glucose levels and food/water intake) and histopathological alterations in the submandibular gland, spleen, and lung were monitored. Proinflammatory cytokines (HMGB1, IFN-γ, IL-17A, BAFF) and SS-related biomarkers (AQP5, KL6) were quantified via enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining.

Results: Our study revealed that UC-MSCs administration significantly reduced B cell infiltration within the submandibular gland (lymphocyte infiltration score: SGL 2.4 ± 0.5 vs. HD-SGL 1.1 ± 0.3, p < 0.001) and downregulated the expression of proinflammatory cytokines in mice with SGL (serum HMGB1: SGL 186.3 ± 24.5 pg/mL vs. HD-SGL 98.7 ± 15.2 pg/mL, p < 0.001; BAFF: SGL 1,245 ± 186 pg/mL vs. HD-SGL 678 ± 95 pg/mL, p < 0.01; IL-17A: SGL 89.4 ± 12.3 pg/mL vs. HD-SGL 48.2 ± 8.6 pg/mL, p < 0.01; IFN-γ: SGL 156.8 ± 22.4 pg/mL vs. HD-SGL 87.3 ± 14.1 pg/mL, p < 0.001). High-dose UC-MSCs (1×10⁶ cells/mouse) exhibited the most pronounced therapeutic effects, demonstrating dose-dependent efficacy.

Conclusions: Our findings highlight UC-MSCs as a potential therapeutic strategy for SGL through the modulation of B cell activity and suppression of proinflammatory cytokines. This study provides preclinical evidence supporting the application of UC-MSCs in managing SS-related glandular dysfunction and emphasizes the necessity of further exploration of their underlying molecular mechanisms.