机构：[1]Department of General Surgery, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai 200072, China[2]Department of Hepatic-biliary-pancreatic surgery, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai 200434, China[3]Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China[4]Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China[5]Central Laboratory, Clinical Medicine Scientific and Technical Innovation Park, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200435, China[6]Department of Metabolic Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China
Severe acute pancreatitis (SAP) is a common abdominal emergency with a high mortality rate and a lack of effective therapeutic options. Although mesenchymal stem cells (MSCs) 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 (NaT) was used to induce a rat SAP model via retrograde injection into the common biliopancreatic duct. After 72 hours of EVs transplantation, pancreatic pathological damage was alleviated, along with a decrease in serum amylase activity and pro-inflammatory cytokines levels. Interestingly, when UCMSCs were preconditioned with 10ng/mL TNF-α for 48h, the obtained EVs (named TNF-α-EVs) performed an enhanced efficacy. Furthermore, both animal and cellular experiments showed that TNF-α-EVs alleviated the necroptosis of acinar cells of SAP via RIPK3/MLKL axis. In conclusion, our study demonstrated that TNF-α-EVs was able to enhance the therapeutic effect on SAP by inhibiting necroptosis compared to normal EVs. This study heralds that TNF-α-EVs may be a promising therapeutic approach for SAP in the future.
基金：
This work was supported by the National Natural Science Foundation
of China [82200717] and Shanghai Fourth People’s Hospital [SY-XKZT-2022-1001,
sykyqd05401].
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|3 区医学
小类|3 区工程：生物医学3 区材料科学：生物材料3 区细胞生物学3 区细胞与组织工程
最新[2025]版：
大类|3 区医学
小类|3 区细胞生物学3 区工程：生物医学4 区细胞与组织工程4 区材料科学：生物材料
第一作者：
第一作者机构：[1]Department of General Surgery, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai 200072, China[2]Department of Hepatic-biliary-pancreatic surgery, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai 200434, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of General Surgery, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai 200072, China[2]Department of Hepatic-biliary-pancreatic surgery, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai 200434, China[*1]Department of Hepatic-biliary-pancreatic surgery, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai 200434, China.[*2]Department of General Surgery, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai 200072, China
推荐引用方式(GB/T 7714)：
Wangcheng Xie,Tingyi Luo,Zhilong Ma,et al.TNF-α preconditioned UCMSCs-derived EVs enhance the inhibition of necroptosis of acinar cells in SAP[J].Tissue engineering. Part A.2023,doi:10.1089/ten.TEA.2023.0139.
APA：
Wangcheng Xie,Tingyi Luo,Zhilong Ma,Shaobo Xue,Xuyang Jia...&Zhenshun Song.(2023).TNF-α preconditioned UCMSCs-derived EVs enhance the inhibition of necroptosis of acinar cells in SAP.Tissue engineering. Part A,,
MLA：
Wangcheng Xie,et al."TNF-α preconditioned UCMSCs-derived EVs enhance the inhibition of necroptosis of acinar cells in SAP".Tissue engineering. Part A .(2023)
