Human Adipose Tissue-Derived Stromal Cells Attenuate the Multiple Organ Injuries Induced by Sepsis and Mechanical Ventilation in Mice
Mechanical ventilation (MV) can augment sepsis-induced organ injury. Previous studies indicate that human mesenchymal stem cells (hMSCs) have immune-modulatory effect. We hypothesize that human adipose tissue-derived stromal cells (hADSCs) could attenuate MV and sepsis-induced organ injury. Male C57BL/6 mice were randomized to five groups: Sham group; MV group; cecal ligation and puncture (CLP) group; CLP + MV group; and CLP + MV + hADSC group. Anesthetized mice were subjected to cecal ligation and puncture surgery. The mice then received mechanical ventilation (12 ml/kg), with or without the intervention of hADSCs. The survival rate, organ injury of the liver and kidney, total protein and cells in bronchoalveolar lavage fluid (BALF), and histological changes of the lung and liver were examined. The level of IL-6 in BALF was measured by ELISA. Real-time quantitative PCR was used to analyze mRNA of IL-6 and tumor necrosis factor-α (TNF-α). hADSC treatment increased survival rate of septic mice with MV. hADSCs attenuated dysfunction of the liver and kidney and decreased lung inflammation and tissue injury of the liver and lung. IL-6 level in BALF and TNF-α and IL-6 mRNA expression in the tissue of the lung, liver, and kidney were significantly reduced by hADSC treatment. MV with conventional tidal volume aggravates CLP-induced multiple organ injuries. hADSCs inhibited the compound injuries possibly through modulation of immune responses.
KEY WORDShuman adipose mesenchymal stem cells sepsis mechanical ventilation
Thanks for Yiteng Liao, Hao Li, and Hongming Zhu’s help during the experiment.
Shuya Mei mainly completed this experiment and wrote this manuscript. Shuang Wang, Shuqing Jin, Xiang Zhao, Zhenzhen Shao, Renlingzi Zhang, and Xiangsheng Yu helped to finish this experiment. Yao Tong and Shibiao Chen have seen the original data. Zhixia Chen and Quan Li modified the final manuscript. All authors approved the final manuscript. Zhixia Chen and Quan Li were responsible for finalizing this manuscript.
Compliance with Ethical Standards
Conflicts of Interest
The authors declare that they have no conflict of interest.
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