Research of Mesenchymal Stem Cell-Derived Microvesicles in Improving Sepsis Ferroptosis Based on Iron Ion Metabolism
ZHENG Danyang
ZHU Huali
FAN Yang
WU Ming
LIU Hui
Abstract：Objective To investigate the therapeutic effects of mesenchymal stem cell(MSC)-derived microvesicles on sepsis by regulating iron ion metabolism to alleviate ferroptosis in endothelial cells.Methods Endothelial cells were di-vided into control group,lipopolysaccharide(LPS)group and MSC-microvesicle group according to the different treat-ment of endothelial cells.Endothelial cells in the control group were untreated;endothelial cells in the LPS group were stimulated with 1 μg/ml LPS for 24 h;endothelial cells in the MSC-microvesicle group were treated with 2 × 106 MSC-mi-crovesicles on the basis of LPS stimulation.Enzyme-linked immunosorbent assay(ELISA)was used to measure interleu-kin 1 beta(IL-1β),IL-6 and tumor necrosis factor alpha(TNF-α)concentrations;reactive oxygen species(ROS)and iron specific kits were used to measure ROS and iron levels of endothelial cells;cell counting kit 8(CCK-8)was used to assess cell proliferation ability;immunofluorescence was used to evaluate lipid peroxidation level;real-time fluorescence quantifi-cation reverse transcription polymerase chain reaction(RT-PCR)was employed to analyze expression of iron metabolism-related genes FPN1,FTH1 and IREB2.Results Compared with the control group,the levels of IL-1β,IL-6,TNF-α and ROS in endothelial cells in LPS group and MSC-microvesicle group increased,and the cell proliferation ability decreased(all P＜0.05);the content of iron ion was reduced and the level of lipid peroxidation significantly increased(all P＜0.05);the expression of FPN1 and FTH1 increased,and the expression of IREB2 decreased(all P＜0.05).Compared with the LPS group,the levels of IL-1β,IL-6,TNF-α and ROS in endothelial cells decreased,and the cell proliferation ability was up-regulated in the MSC-microvesicles group(all P＜0.05);the content of iron ion was reduced and the level of lipid peroxidation decreased(all P＜0.05);the expression of FPN1 and FTH1 decreased,and the expression of IREB2 increased(all P＜0.05).Conclusion Endothelial cells undergo ferroptosis during sepsis,and MSC-microvesicles alleviate this process by modula-ting iron metabolism.
Keywords：SepsisMesenchymal stem cell-derived microvesiclesEndothelial cellFerroptosisIron ion metabo-lism
Publication Date：2025-07-28
Online Publishing Date：2025-08-27(First online date of this platform, not the publication date of the document)
Pages：6( 560-564,584 )