解放军医学院学报2025，Vol.46Issue(10)：960-971,12.DOI:10.12435/j.issn.2095-5227.25040402
人脂肪间充质干细胞源凋亡囊泡促进中性粒细胞炎性坏死转变为中性粒细胞凋亡的研究
Apoptosis vesicles from human adipose-derived mesenchymal stem cells promote neutrophil apoptosis over inflammatory necrosis
摘要
Abstract
Background Mesenchymal stem cell-derived apoptotic vesicles(MSCs-apoVs)have demonstrated the capacity to promote apoptosis in polymorphonuclear neutrophils(PMNs)and reduce their neutrophilic inflammatory necrosis(NETosis).Consequently,MSCs-apoVs have emerged as a novel therapeutic strategy for inhibiting NETs formation by suppressing NETosis in PMNs and enhancing their apoptotic processes.Objective To investigate the effects of adipose-derived stem cell-derived apoptotic vesicles(ADSCs-apoVs)on promoting PMNs apoptosis and inhibiting NETosis.Methods Primary mouse bone marrow-derived polymorphonuclear neutrophils(PMNs)were isolated via differential centrifugation combined with sterile fluorescence-activated cell sorting(FACS).PMNs were co-cultured with adipose-derived stem cell apoptotic vesicles(ADSCs-apoVs)at varying concentrations(1,5,and 10 μg/mL)for 8 hours.NETs formation,NETosis,and apoptosis were quantified using immunofluorescence and flow cytometry.Results ADSCs-apoVs regulated PMNs fate through dual pathways.NETosis suppression showed that at 5 μg/mL,significant reductions occurred in H3cit production(48.20±0.96 vs 75.30±1.00,P＜0.001),NETosis incidence(36.07%±3.07%vs control 57.03%±5.35%,P=0.002);At 10 μg/mL,synergistic inhibition was observed for H3cit levels(24.73±0.90 vs 75.30±1.00,P＜0.001),NETosis incidence(16.48%±8.09%vs 57.03%±5.35%,P＜0.001).Apoptosis threshold effect showed that 10 μg/mL elevated total apoptosis(50.70%±10.86%vs 10.30%±1.55%,P=0.001),early apoptosis(14.30%±1.97%vs 0.25%±0.21%,P＜0.001),late apoptosis(36.40%±12.75%vs 10.06%±1.40%,P=0.011).No significant apoptosis changes occurred at≤5 μg/mL(10.26%±7.31%vs 10.30%±1.55%,P＞0.999),1μg/mL(9.14%±4.82%vs 10.30%±1.55%,P=0.997).Conclusion ADSCs-apoVs regulate PMNs fate through dual pathways by inhibiting histone H3 citrullination to suppress NETs formation,thereby preventing NETosis,and concurrently activating apoptosis pathways to induce extensive PMNs apoptosis.5 μg/mL ADSCs-apoVs defines a therapeutic window for NETosis-selective inhibition,while 10 μg/mL represents an effective clearance dose for synergistic NETosis suppression and apoptosis activation.关键词
脂肪间充质干细胞/细胞凋亡/凋亡囊泡/中性粒细胞胞外诱捕网/中性粒细胞炎性坏死Key words
adipose-derived mesenchymal stem cells/cell apoptosis/apoptotic vesicles/neutrophil extracellular traps/neutrophilic inflammatory necrosis分类
医药卫生引用本文复制引用
宫晓静,祖潇然,景志强,张俊雅,徐亦驰,韩岩..人脂肪间充质干细胞源凋亡囊泡促进中性粒细胞炎性坏死转变为中性粒细胞凋亡的研究[J].解放军医学院学报,2025,46(10):960-971,12.基金项目
北京市自然科学基金青年项目(7244299) （7244299）
