Immunomodulatory and Protective Effects of Stem Cells from Human Exfoliated Deciduous Teeth on Mice with Sepsis

Background: Sepsis characterized by an uncontrolled inflammatory response is a common clinical syndrome which can cause organ dysfunction, shock, and often death. Importantly, no specific treatment for sepsis exists. Little is known about the therapeutic effects of stem cells from human exfoliated deciduous teeth (SHEDs) on sepsis. The study aims to investigate immunomodulatory and protective effects of SHEDs against sepsis. Methods: Polymicrobial sepsis was induced in mice via cecal ligation and puncture (CLP). SHEDs or normal saline was intravenously injected 30 min after CLP. Seventy-five adult male C57BL/6 mice were randomized into three groups (n = 25/group): (1) Sham-CLP; (2) CLP; (3) CLP+SHED. Mice (20/group) were monitored for 96 h post-CLP for survival. Five mice/group were euthanized at 24 h post-CLP; blood and tissues (lung, liver, kidney, spleen, and intestine) were harvested for pathophysiological study. A cytometric bead array assay was employed to assess plasma concentrations of cytokines [interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), monocytechemoattractant protein -1 (MCP-1), IL-10], and an automatic biochemical analyzer was used to assess liver and kidney function. Hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining were performed to evaluate organ injuries. Immunofluorescence staining and E. coli colony-forming units (CFUs) counts of the spleen were also employed. Results: Kaplan-Meier survival analysis revealed a significantly lower survival rate in CLP than in Sham-CLP mice, and a significantly better survival rate in CLP+SHED mice than in CLP mice (p = 0.021). At 24 h post-CLP, serum IL-6, MCP-1, TNF-alpha, and IL-10 were significantly lower in the CLP+SHED group than in the CLP group (allp < 0.05). When compared to CLP mice, CLP+SHED mice had altered distribution of cluster of differentiation 3+ (CD3+) T cells and CD11c+ dendrocytes in the spleen, decreased the number of TUNEL+ cells in the kidneys and lungs, and altered TUNEL+ cell distribution in the intestine and spleen. Compared to CLP mice, TUNEL+ cells in kidney, lung and spleen of CLP-SHEDs group were attenuated although without significance (p = 0.079, 0.045 and 0.075 respectively). However, the distribution of TUNEL+ cells in intestine were altered in CLP+SHED mice when compared to CLP mice. The E. coli clearance in spleen was improved (p = 0.075) in the CLP+SHED mice when compared to CLP group. Conclusions: SHEDs treatment 30 min after sepsis induction improves survival in mice with CLP-related sepsis. It has potential to be a new therapeutic option for sepsis.