Adipose-derived mesenchymal stem cells ameliorate acute liver injury in rat model of CLP induced-sepsis via sTNFR1

Huoyan Liang, Xianfei Ding, Yanwu Yu, Haibo Zhang, Lexin Wang, Quancheng Kan, Shanshan Ma, Fangxia Guan, Tongwen Sun

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Sepsis is characterized as exceed inflammation response and multiple organs dysfunction. Many articles suggested that mesenchymal stem cells can alleviate the inflammation and improve the survival rate of inflammatory animal models, however, the mechanism is still unclear. This study aimed to test the hypothesis that rat adipose-derived mesenchymal stem cells (ADMSCs) produce a amount of soluble tumour necrosis factor receptor 1 (sTNFR1), which ameliorated liver injury and inflammation and increased the survival rate of septic rat model.120 adult male Sprague-Dawley rats were randomly divided into 4 groups: sham-operated (Sham), sepsis-induced by cecal ligation and puncture (CLP), shNC (injected 1 × 106 ADMSCs with transfected with scramble shRNA 1 h after CLP), and shsTNFR1 (injected 1 × 106 ADMSCs with transfected with sTNFR1 1 h after CLP). The serum sTNFR1 levels were the lowest in Sham and highest in shNC group. ADMSCs could decrease the levels of pro-inflammatory cytokines such as TNF-α, IL-6, AP-1 c-jun and NF-κB p56 after CLP administration, whereas this result was weaken by shsTNFR1 administration. Moreover, shNC had an increased levels of the anti-inflammatory factor IL-10 compared with CLP, and this change could be weakened in shsTNFR1 administration. More importantly, ADMSCs could improve the survival rate of CLP-induced septic rats. Therapeutically administered ADMSCs secrete sTNFR1, which alleviated the liver injury and inflammatory response. Additionally, ADMSCs also ameliorated the systematic inflammation and increased the survival rate of septic rats.

Original languageEnglish (US)
Article number111465
JournalExperimental Cell Research
Volume383
Issue number1
DOIs
StatePublished - Oct 1 2019

Keywords

  • Liver injury
  • Sepsis
  • Soluble tumour necrosis factor receptor 1
  • Stem cells

ASJC Scopus subject areas

  • Cell Biology

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