Gingival mesenchymal stem cell-derived exosomal miR-23a-3p targets IL-6R to attenuate autoimmune insulitis: a cell-free therapeutic strategy for type 1 diabetes

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Type 1 diabetes (T1D) is characterized by autoimmune destruction of pancreatic β-cells, yet current therapies fail to address immune dysregulation. Gingival mesenchymal stem cells (GMSC) exhibit immunomodulatory potential, but cell-based therapies face challenges in standardization and survival. Exosomes, nanosized vesicles delivering bioactive molecules like miRNAs, offer a cell-free alternative. This study investigates GMSC-derived EXO (GMSC-EXO) enriched with miR-23a-3p as a novel strategy to attenuate T1D progression. Methods Spontaneous T1D in NOD/LtJ mice was treated with GMSC-EXO. Exosome secretion was inhibited using GW4869, and miR-23a-3p was knocked down via LV3-miR-23a-3p inhibitor. Blood glucose, pancreatic inflammation, and immune cell dynamics were monitored in vivo. CD4 + T-cell subsets (Th1/Th17, Tregs) and cytokine levels were analyzed via flow cytometry and ELISA. Dual-luciferase assays and Western blot validated miR-23a-3p targeting of IL-6R and downstream IL-6R/JAK1/STAT3 signaling. Results GMSC-EXO delayed hyperglycemia progression and improved survival. Depleting exosomes or miR-23a-3p diminished therapeutic efficacy. Mechanistically, miR-23a-3p directly silenced IL-6R, suppressing IL-6R/JAK1/STAT3 signaling, reducing Th1/Th17 infiltration, and expanding Tregs and IL-10 + cells. In vitro, GMSC-EXO reduced IFN-γ/IL-17 A and elevated IL-10, effect

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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