三维微环境手性特征调控间充质干细胞线粒体功能  

Chirality controls mitochondrial function of mesenchymal stem cells in three-dimensional microenvironment

作　　者：何颖[1] 冯传良[2] 刘进营 郑慧敏 江圣杰 He Ying;Feng Chuanliang;Liu Jinying;Zheng Huiming;Jiang Shengjie(Department of Geriatric Dentistry,Peking University School and Hospital of Stomatology, Beijing 100034, China;State Key Laboratory of Metal Matrix Composites School of Materials Science and Engineering, Shanghai Jiaotong University, Shanghai 200030, China;Key Laboratory for Special Functional Materials of Ministry of Education School of Materials Science and Engineering, Henan University, Zhengzhou 450001, China)

机构地区：[1]北京大学口腔医院特诊科,北京100034 [2]上海交通大学材料科学与工程学院,上海200030 [3]河南大学材料学院特种功能实验室,郑州450001

出　　处：《首都医科大学学报》2022年第3期440-445,共6页Journal of Capital Medical University

基　　金：国家自然科学基金(51833006,82101072,52003072)。

摘　　要：目的解析手性微环境介导线粒体功能调控骨髓间充质干细胞成骨分化。方法体外通过三维手性微环境培养间充质干细胞监测干细胞的线粒体膜电位功能,在体内观察凝胶植入后早期缺损区域关键调控线粒体功能趋化CXCL2因子的表达,体外高通量组学分析相关线粒体与代谢信号通路的差异。结果免疫荧光染色显示右旋手性基质中线粒体线粒体深红色荧光探针染色比例降低,表明右旋手性基质中的干细胞线粒体膜电位出现损伤。大鼠颅骨缺损模型发现在早期植入三维手性凝胶后左旋组修复区域的CXCL2明显表达上调。京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析发现线粒体相关基因与多个信号通路发生了明显的差异表达。差异基因分析发现右旋组中间充质干细胞出现了线粒体降解相关基因的表达上调。左旋手性基质能上调干细胞线粒体NADH脱氢酶活性,右旋手性基质中间充质干细胞线粒体功能出现明显功能损伤。结论生物植入材料基质手性具备调控干细胞线粒体功能能力。Objective To analyze the chirality mediated mitochondrial function of stem cells and regulation of osteogenic differentiation.Methods Mesenchymal stem cells(MSCs)were cultured in vitro to monitor the mitochondrial membrane potential function of stem cells in vitro.In vivo,the expression of CXCL2 factor was observed in the early defect area after hydrogel implantation,and the difference between the related mitochondria and metabolic signaling pathways was analyzed by high throughput analysis in vitro.Results The proportion of mitotracker deep red immunoflourence staining decreased in the righ-handed group,which indicated that the mitochondrial membrane potential of stem cells was damaged in the right-handed group.In the rat cranial defects model,the expression of CXCL2 in the left-handed matrix repair area was up-regulated after early implantation.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis found that mitochondrial related genes and signaling pathways were significantly differentially between different chiral groups.A global microarray gene analysis showed that the expression of mitochondrion degradation related genes up-regulated in right-handed group.The results showed that left-handed matrix could up regulate the mitochondrial NADH dehydrogenase expression,while the mitochondrial function of mesenchymal stem cells in right-handed matrix was significantly damaged.Conclusion The chirallity of biological implant materials was able to regulate the function of stem cell mitochondria.

关 键 词：手性 线粒体 间充质干细胞 

分 类 号：Q731[生物学—分子生物学]