肿瘤坏死因子 α 预处理的脐带间充质干细胞来源细胞外囊泡增强对重症急性胰腺炎腺泡细胞坏死性凋亡的抑制

Severe acute pancreatitis (SAP) is a common abdominal emergency with a high mortality rate and a lack of effective therapeutic options. Although mesenchymal stem cell (MSC) transplantation is a potential treatment for SAP, the mechanism remains unclear. It has been suggested that MSCs may act mainly through paracrine effects; therefore, we aimed to demonstrate the therapeutic efficacy of extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (UCMSCs) for SAP.

Na-taurocholate was used to induce a rat SAP model through retrograde injection into the common biliopancreatic duct. After 72 h of EVs transplantation, pancreatic pathological damage was alleviated, along with a decrease in serum amylase activity and pro-inflammatory cytokine levels. Interestingly, when UCMSCs were preconditioned with 10 ng/mL tumor necrosis factor alpha (TNF- ) for 48 h, the obtained EVs (named TNF- -EVs) performed an enhanced efficacy.

Furthermore, both animal and cellular experiments showed that TNF- -EVs alleviated the necroptosis of acinar cells of SAP through RIPK3/MLKL axis.

In conclusion, our study demonstrated that TNF- -EVs were able to enhance the therapeutic effect on SAP by inhibiting necroptosis compared to normal EVs.

This study heralds that TNF- -EVs may be a promising therapeutic approach for SAP in the future.