低氧和氧化应激对不同来源间充质干细胞旁分泌的差异性影响  

Differential effects of hypoxia and oxidative stress on paracrine of mesenchymal stem cells from different sources

作　　者：潘筱颖 许永德 刘志强[4] 邢晓雯 杨勇 Pan Xiaoying;Xu Yongde;Liu Zhiqiang;Xing Xiaowen;Yang Yong(Changchun University of Chinese Medicine,Changchun 130117,Jilin Province,China;Department of Urology,Affiliated Hospital of Changchun University of Chinese Medicine,Changchun 130021,Jilin Province,China;Beijing Friendship Hospital,Capital Medical University,Beijing 100000,China;Institute of Military Medicine,Academy of Military Sciences,Beijing 100000,China)

机构地区：[1]长春中医药大学,吉林省长春市130117 [2]长春中医药大学附属医院泌尿外科,吉林省长春市130021 [3]首都医科大学附属北京友谊医院,北京市100000 [4]军事科学院军事医学科学院,北京市100000

出　　处：《中国组织工程研究》2024年第19期3024-3030,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(8197051689),项目负责人:刘志强。

摘　　要：背景:间充质干细胞的生物学行为受所处生存微环境的影响,微环境条件预处理是调控间充质干细胞功能的重要手段。目的:对比氧化应激和低氧条件下脐带间充质干细胞、脂肪间充质干细胞旁分泌功能的差异,为治疗不同疾病选择适当的间充质干细胞预处理方式提供理论依据。方法:培养脐带间充质干细胞和脂肪间充质干细胞,分别加入不同浓度的H_(2)O_(2)或不同体积分数的O_(2)干预,检测细胞形态、增殖、活力和旁分泌因子表达。结果与结论:①普通培养环境下,脐带间充质干细胞中脑源性神经营养因子和转化生长因子β的表达水平显著高于脂肪间充质干细胞,而脂肪间充质干细胞中基质细胞衍生因子1α和肿瘤坏死因子刺激因子6的表达水平显著高于脐带间充质干细胞;②中低浓度水平(≤100μmol/L)H_(2)O_(2)对2种间充质干细胞活力的影响无显著差异,但H_(2)O_(2)浓度从50μmol/L增至100μmol/L使脐带间充质干细胞中血管内皮生长因子表达水平显著增高,脂肪间充质干细胞中碱性成纤维细胞生长因子、血管内皮生长因子、基质细胞衍生因子1α和白细胞介素10表达水平均显著升高;③体积分数1%O_(2)促进2种间充质干细胞增殖;体积分数1%O_(2)干预24 h后,2种间充质干细胞中基因表达水平均有升高,但脂肪间充质干细胞中血管内皮生长因子、白细胞介素10和肿瘤坏死因子刺激因子6的表达水平显著高于脐带间充质干细胞;④结果提示:低氧和氧化应激预处理可提高间充质干细胞旁分泌功能,但2种间充质干细胞对低氧和氧化应激的响应不同,治疗疾病可选择适合的间充质干细胞预处理方式进一步提升其治疗潜力。BACKGROUND:The biological behavior of mesenchymal stem cells is influenced by the survival microenvironment.Pre-treatment of the microenvironment is an important means of regulating the function of mesenchymal stem cells.OBJECTIVE:To compare the differences in paracrine function of umbilical cord mesenchymal stem cells and adipose mesenchymal stem cells under oxidative stress and hypoxia,and to provide a theoretical basis for selecting appropriate pretreatment of mesenchymal stem cells to treat different diseases.METHODS:Umbilical cord mesenchymal stem cells and adipose mesenchymal stem cells were cultured by H_(2)O_(2)or O_(2)oxygen,respectively,and cell morphology,proliferation,viability and paracrine factor expression were examined.RESULTS AND CONCLUSION:(1)The expression levels of brain-derived neurotrophic factor and transforming growth factor-βwere higher in umbilical cord mesenchymal stem cells than in adipose mesenchymal stem cells under a normal culture environment,while the expressions of stromal cell-derived factor-1αand tumor necrosis factor stimulating factor-6 in the adipose mesenchymal stem cells were significantly higher than those in the umbilical cord mesenchymal stem cells.(2)There was no significant difference in the effect of low and moderate levels(≤100μmol/L)of H_(2)O_(2)on the viability of the two mesenchymal stem cells.However,increasing the H_(2)O_(2)concentration from 50μmol/L to 100μmol/L resulted in a distinct increase in vascular endothelial growth factor expression in umbilical cord mesenchymal stem cells.The expression of basic fibroblast growth factor,vascular endothelial growth factor,stromal cell-derived factor-1αand interleukin-10 in adipose mesenchymal stem cells was greatly increased by increasing H_(2)O_(2)concentration in this range.(3)1%O_(2)hypoxia promoted mesenchymal stem cell proliferation.After 24 hours of culture in 1%O_(2),gene expression levels were elevated in both mesenchymal stem cells,but the expression levels of vascular endothelial growth factor,inter

关 键 词：脐带间充质干细胞 脂肪间充质干细胞 旁分泌 氧化应激 低氧 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] Q291[生物学—细胞生物学]