RETRACTED: Adipose‐derived mesenchymal stem cells ameliorate the inflammatory reaction in CLP‐induced septic acute lung injury rats via sTNFR1

Abstract

We hypothesized that the adipose‐derived mesenchymal stem cells (ADMSCs), which secrete high amounts of soluble molecules, such as soluble tumor necrosis factor receptor 1 (sTNFR1), may ameliorate sepsis‐induced acute lung injury (ALI). A total of 120 male adult Sprague–Dawley rats were separated into four groups: the sham control (SC), sepsis induced by cecal ligation and puncture (CLP), CLP–ADMSCs, and CLP–sTNFR1 small interfering RNA (siRNA) groups; CLP groups underwent CLP and then received 1 × 106 ADMSCs with or without knockdown of sTNFR1 intravenously at 1 hr after surgery. Rats were killed at 3, 6, 24, and 48 hr after the SC or CLP procedures. 5‐Ethynyl‐2′‐deoxyuridine‐labeled ADMSCs extensively colonized the lungs at 6, 24, and 72 hr after injection. The lung wet/dry (W/D) weight ratios in the CLP group were higher than those in SC group; however, ADMSCs ameliorated the W/D weight ratios following CLP, and this effect was abolished by sTNFR1 siRNA treatment. The levels of serum sTNFR1 and interleukin‐10 (IL‐10) were higher in the CLP–ADMSCs group and lower in the SC group than in other groups; interestingly, these levels were higher in CLP and CLP–sTNFR1 siRNA groups than in SC group. Tumor necrosis factor‐α and IL‐6 levels increased significantly after CLP, and ADMSCs could alleviate these changes, but the effect was weakened by sTNFR1 siRNA treatment. The lung cell apoptosis and edema levels were consistent with IL‐6 levels among all groups. Therapeutically administered ADMSCs secrete sTNFR1, which most likely protects against ALI in septic rats by ameliorating inflammation and lung edema.

Adipose-Derived Mesenchymal Stem Cells Attenuate Acute Lung Injury Through Regulation of the Gut Microbiota in Septic Rats

“…Intervention with ADMSCs reduced organ damage, as well as inflammatory infiltration and hemorrhage, in the lungs, and the diversity of the flora and the content of pathogenic bacteria in rats with sepsis increased significantly. In addition, we found that treatment with ADMSCs also reduced the expression of pro-inflammatory factors, such as TNF-α and IL-6, which is consistent with our previous studies [49,50] .…”

Efficacy of mesenchymal stem cell therapy for sepsis: A meta-analysis of preclinical studies

“…A previous meta-analysis [42] collected and evaluated preclinical evidence regarding the use of MSCs in animal models of sepsis and demonstrated that MSC therapy could reduce the odds of death. The updated meta-analysis presented here includes another seven high-quality studies [27,[29][30][31][32][33]41] that were mainly published in recent 3 years, and confirms the potential therapeutic efficacy of MSCs for reducing the mortality rate of sepsis in animal models, thus, providing possibilities for MSC therapy in preclinical studies of sepsis. To our knowledge, two small clinical phase 1 trials [43,44] have been performed to evaluate the safety and feasibility of MSC therapy in sepsis and septic shock patients.…”

“…Firstly, our study provides an up-to-date meta-analysis of the effectiveness of MSCs in sepsis animal models. Although a previously published metaanalysis [42] assessed the effectiveness of MSCs in sepsis animal models, the meta-analysis presented here includes seven recently published high-quality studies [27,[29][30][31][32][33]41]. Out of all the included studies, only one study showed no positive effect of MSC therapy on sepsis animal models (OR=2.78, 95% CI 0.66-11.62, P<0.001).…”

Efficacy of mesenchymal stem cell therapy for sepsis: A meta-analysis of preclinical studies

“…A previous meta-analysis [38] collected and evaluated preclinical evidence regarding the use of MSCs in animal models of sepsis and demonstrated that MSC therapy could reduce the odds of death. The updated meta-analysis presented here includes another seven high-quality studies [27,36,37,[39][40][41][42] that were mainly published in the last three years, and confirms the potential therapeutic efficacy of MSCs for reducing the mortality rate of sepsis in animal models, thus, providing possibilities for MSC therapy in preclinical studies of sepsis. To our knowledge, two small clinical phase 1 trials [43,44] have been performed to evaluate the safety and feasibility of MSC therapy in sepsis and septic shock patients.…”

“…Firstly, our study provides an upto-date meta-analysis of the effectiveness of MSCs in sepsis animal models. Although a previously published meta-analysis [38] assessed the effectiveness of MSCs in sepsis animal models, the meta-analysis presented here includes seven recently published high-quality studies [27,36,37,[39][40][41][42].…”