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Therapeutic Efficacy of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Septic Mice
Song Yuqing1, Zhu Ming1, He Xiao1, Guo Wei1, Xing Wei1, Liang Donglan1, An Tianchen1, Ao Luoquan1, Huang Hong1, Jiang Dongpo2*, Xu Xiang1*
1State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Surgery Research Chongqing 400042, China; 2ICU, Daping Hospital, the Third Military Medical University, Chongqing 400042, China
Abstract: The aim of this study was to evaluate the therapeutic efficacy of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in septic mice. A total of 90 C57BL/6 mice with cecal ligation and puncture (CLP)-induced sepsis were randomly divided into 3 groups, i.e. PBS treating group (CLP+PBS), hUC-MSCs treating group (CLP+hUC-MSCs), and Sham group treated with sham surgery, then PBS (Sham+PBS). PBS and hUC-MSCs suspension (7.5×105 cells/mL) were administered via tail vein injection in a volume of 0.2 mL per mouse at 3 h after CLP or sham surgery. All mice received subcutaneous injection of antibiotics at 6 h and 18 h after surgery. At 24 h after surgery, the abundance of neutrophils in peripheral blood and in peritoneal lavage fluid, serum inflammatory cytokines, and serum markers of liver and kidney function were analyzed by flow cytometry, ELISA, and biochemical tests, respectively. Meanwhile, the pathological changes in liver, kidney and lung were assessed by the HE (hematoxylin and eosin) staining. The survival rates of mice in each group were evaluated every 12 h till 120 h, and then the survival curves were plotted. The mouse model of sepsis in this study was reproducible. When compared to PBS-treated mice, hUC-MSCs-treated mice showed a significant decrease in the ratios of serum pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) to an anti-inflammatory cytokine (IL-10) and an obvious improvement in survival and general status. And, it could reduce polymorphonuclear neutrophils infiltration. The levels of serum markers of liver and kidney function (ALT, AST, Crea and Urea) and the pathologic lesion of organs (liver, kidney and lung) were significantly lower in hUC-MSC-treated mice than that in PBS-treated mice. Xenotransplantation of hUC-MSCs into CLP-induced septic mice showed an obvious protective effect.