Gingival-Derived Mesenchymal Stem Cells Protect Against Sepsis and Its Complications

OBJECTIVE: In the present study, we separated and characterized mouse gingival-derived mesenchymal stem cells (GMSCs) and investigated whether GMSCs can improve lipopolysaccharide (LPS)-induced sepsis and its complications. METHODS: Ninety-six ICR mice were randomly divided into the following groups: the control (Sham), LPS, and LPS + MSC groups. Mice received 5 mg/kg LPS intraperitoneally to induce sepsis. Histopathological micrographs illustrated organ injury. We detected systemic inflammation, blood glucose levels, and serum levels of high-mobility group box 1 (HMGB1) and lactate. In addition, pulmonary inflammation, lung permeability, and oxidative stress-related indicators in lung tissue were measured. RESULTS: We successfully separated a novel population of MSCs from mouse gingiva. These cells had MSC-associated properties, such as a typical fibroblast-like morphology, multiple differentiation potential, and certain phenotypes. Cell-based therapy using GMSCs significantly improved the survival rate, systemic inflammation, hypoglycemia, multiple organ dysfunction syndrome (MODS), and aortic injury during sepsis. GMSCs administration reduced pulmonary inflammation, lung permeability, and oxidative stress injury. GMSCs administration reduced neutrophil infiltration partly because GMSCs inhibited neutrophil chemoattractants tumor necrosis factor (TNF-α), C-X-C motif chemokine ligand (CXCL-1), and Interleukin (IL-8). GMSCs impaired LPS-induced HMGB1 and lactate release during sepsis. CONCLUSION: GMSCs administration is a novel therapeutic strategy targeting aerobic glycolysis for the treatment of sepsis because GMSCs impair LPS-induced HMGB1 and lactate release. GMSCs alleviate lung injury partly because GMSCs exert immune effects, inhibit neutrophilic inflammation, and reduce oxidative stress injury.