Mechanism of human umbilical cord mesenchymal stem cell-derived exosomes against mouse renal ischemia/reperfusion injury
- VernacularTitle:人脐带间充质干细胞来源外泌体抗小鼠肾缺血再灌注损伤的机制
- Author:
Lingyu LI
1
;
Huafeng WEI
;
Hao LUO
;
Hao WANG
;
Jiahui HE
;
Yawei YAO
;
Xinghua LYU
Author Information
- Publication Type:Journal Article
- Keywords: human umbilical cord mesenchymal stem cell; exosome; AMPK-YAP1 pathway; apoptosis; kidney; ischemia/reperfusion injury
- From: Chinese Journal of Tissue Engineering Research 2025;29(13):2706-2712
- CountryChina
- Language:Chinese
- Abstract: BACKGROUND:Human umbilical cord mesenchymal stem cell-derived exosomes are involved in multiple injury repair processes,and the effects and the specific mechanisms of renal ischemia/reperfusion injury have not been fully elucidated.OBJECTIVE:To investigate the molecular mechanism of human umbilical cord mesenchymal stem cell-derived exosomes in the treatment of renal ischemia/reperfusion injury.METHODS:(1) Human umbilical cord mesenchymal stem cells were cultured and exosomes were obtained and identified using an exosome extraction kit.(2) The distribution of exosomes in the kidney of mice with renal ischemia/reperfusion injury was examined by intravital fluorescence imaging.(3) Thirty C57/BL6 male mice were divided into five groups according to the random number table method:sham operation group,renal ischemia/reperfusion group,sham operation group+Compound C group,renal ischemia/reperfusion+exosome group (exosome group),and renal ischemia/reperfusion+exosome+Compound C group (exosome+Compound C group),with 6 mice in each group.Except the sham operation group,bilateral renal pedicles were clamped for 45 minutes and a mouse model of renal ischemia/reperfusion injury was established after 24 hours of reperfusion.In sham operation+Compound C group and exosome+Compound C group,AMPK inhibitor Compound C was intraperitoneally injected 30 minutes before model establishment.In the exosome group and exosome+Copmpound C group,exosomes were injected through the tail vein 15 minutes before renal pedicle clipping.The levels of serum creatinine and urea nitrogen,interleukin 6,and tumor necrosis factor α in renal tissue,and the expression of apoptosis-related factors in renal tissue were detected after 24 hours of reperfusion in each group.RESULTS AND CONCLUSION:(1) Human umbilical cord mesenchymal stem cell exosomes had the typical tea tray morphology,with the diameter distribution in the range of 40-160 nm,and expressed the specific marker membrane protein of exosome surface.(2) Murine kidneys after renal ischemia/reperfusion injury were more likely to gather human umbilical cord mesenchymal stem cell exosomes compared with the sham operation group.(3) Exosome pretreatment reduced renal injury and the level of renal cell apoptosis in mice treated with renal ischemia/reperfusion injury.Moreover,this protective effect could be reversed by AMPK inhibitors.These findings verify that human umbilical cord mesenchymal stem cell-derived exosomes exerting a protective effect on renal ischemia/reperfusion injury may be related to the activation of the AMPK/YAP1 pathway to antiapoptosis.
