BACKGROUND: Sepsis with acute respiratory distress syndrome (ARDS) is a fatal disease, and is usually treated by supporting therapy, which can improve prognosis, but not obviously. Therefore, searching a novel effective method is urgent. Mesenchymal stem cells with multilineage differentiation have been shown to be effective in the treatment of various diseases.
OBJECTIVE: To discuss the protective effect of adipose tissue-derived mesenchymal stem cells (AD-MSCs) on ARDS complicated by sepsis and its underlying mechanism.
METHODS: (1) AD-MSCs were isolated by tissue adherent culture from rats. (2) Adult male Sprague-Dawley rats provided by Laboratory Animal Center of Lanzhou University, China were randomly divided into normal saline control group (group A), normal saline+AD-MSCs group (group B), sepsis+ARDS group (group C), sepsis+ARDS+AD-MSCs group (group D) (n=10 per group). (3) Rats in the groups A and B were taken out of the cecum after laparotomy, which was then put back into the abdominal cavity that was sutured hereupon. Caudal intravenous injection of normal saline (1.0 mL) or normal saline+AD-MSCs (1.2×106) was performed 12 hours later. In the groups C and D, cecal ligation and puncture were performed, ARDS was induced by 100% oxygen inhalation for 48 hours, and then caudal intravenous injection of normal saline (1.0 mL) or AD-MSCs (1.2×106 ) was implemented at 12 hours after modeling. (4) The arterial oxygen saturation was detected at 24 hours after modeling. The lung wet/dry ratio was calculated at 48 hours after modeling. The levels of inflammatory cytokines in lung tissue were detected by ELISA. The pathological changes in lung tissue were observed using hematoxylin-eosin staining. Nuclear factor-κB activity and mRNA and protein levels of toll-like receptors 2 and 4 in lung tissue were determined by electrophoretic mobility shift assay, RT-PCR and western blot assay, respectively．
RESULTS AND CONCLUSION: Compared with the groups A and B, in the group C, the lung wet/dry ratio, lung injury score, levels of inflammatory cytokines, nuclear factor-κB activity, mRNA and protein levels of toll-like receptors were significantly increased, and the arterial oxygen saturation was significantly decreased (P < 0.05). Compared with the group C, in the group D, there was a significant decrease in the lung wet/dry ratio, lung injury score, levels of pro-inflammatory factors (tumor necrosis factor α, interleukin 1β, interleukin 6), nuclear factor-κB activity, mRNA and protein levels of toll-like receptors, and a significant increase in the arterial oxygen saturation and level of anti-inflammatory factor (interleukin 10) (P < 0.05). There were no significant differences in each index between groups A and B (P > 0.05). In the groups A and B, pathological changes in the lung were not obvious under light microscope. In the group C, there was significant lung hyperemia and edema fluid; red blood cells and inflammatory cells in the alveolar cavity were also detected. In the group D, lung damages that mentioned above were alleviated. These results indicate that AD-MSCs can down-regulate the levels of inflammatory factors, reduce lung injury possibly through inhibiting toll-like receptors/nuclear factor-κB signaling pathway in septic rats with ARDS．
中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程