Prolongs sepsis by promoting glutathione synthesis

backdrop

Mesenchymal stem cells (MSCs) have the ability to alleviate multiple organ failure (MOF) and reduce sepsis mortality.

The survival of MSCs is severely limited due to oxidative stress responses triggered by excessive sepsis inflammation.

Previous studies have shown that cytokine stimuli such as IL-1β, TNF-α, and IFN-γ can enhance the paracrine action of MSCs, a process known as inflammatory licensing.

This enhancement may potentially lead to apoptosis of mesenchymal stem cells.

Glutathione (GSH) plays a key role in maintaining cell homeostasis. Studies have shown that glutathione can effectively bind and neutralize excess peroxides in cells, including H2O2 and ROS, through the action of glutathione transferase (GST).

Inhibiting premature senescence of bone marrow mesenchymal stem cells and maintaining their REDOX homeostasis are essential conditions for effective treatment of sepsis with bone marrow mesenchymal stem cells.

aim

To investigate the therapeutic effect and mechanism of lycium oligosaccharide (FLO) -nasal mucosal ectodermal mesenchymal stem cells (EMSCs) on sepsis rats.

method

The macrophage lipid raft chromatography prepared in the laboratory was used to screen FLO from 21 different Chinese herbal sugars.

EMSCs transfected with and without FLO were compared by RNA-seq.

Cecal ligation puncture (CLP) was performed in CLP group, EMSCs group and FL-EMSCs group (n = 10).

In NC group, cecal ligation was performed without puncture.

The therapeutic effects of EMSCs and FL-EMSCs on sepsis rats were evaluated by RT-PCR, western blot and histochemical staining.

result

FLO promoted the M2 polarization of macrophages and enhanced the paracrine effect of EMSCs, but did not induce apoptosis.

FLO promotes the synthesis of GSH in EMSCs, helping to remove reactive oxygen species (ROS) within these cells.

Flo-treated EMSCs show enhanced protection against macrophage pyrodeath, thereby preventing immune paralysis during sepsis.

conclusion

The article expounds the following points:

• (1) The structure of FLO and its mechanism of promoting EMSCs secretion paracrine;
• (2) FLO enhances the antioxidant capacity of EMSCs by promoting the synthesis of GSH;
• (3) FLO-EMSCs can improve the survival rate of sepsis model by inhibiting macrophage pyrodeath and promoting macrophage M2 polarization.

This study proposes an innovative method to enhance the anti-inflammatory properties of MSCs using oligosaccharides of traditional Chinese medicine, thereby improving their therapeutic efficacy in a sepsis model.

reference

Yu Q, Zhang L, Wang Z, et al. Anti-inflammatory oligosaccharide licensed mesenchymal stem cells allow prolonged survival of septic rats via the promotion of glutathione synthesis. Phytomedicine. Published online October 22, 2024. doi:10.1016/j.phymed.2024.156173