周期性牵张应变对大鼠骨髓间充质干细胞神经向分化的影响  

Effects of Cyclic Strain on Neural Differentiation of Rat Bone Marrow-Derived Mesenchymal Stem Cells

作　　者：程虹 黄艳 姚杰 陈伟 钱佳怡 樊瑜波 CHENG Hong;HUANG Yan;YAO Jie;CHEN Wei;QIAN Jiayi;FAN Yubo(Beijing Advanced Innovation Center for Biomedical Engineering,Key Laboratory of Biomechanics and Mechanobiology,Ministry of Education,School of Biological Science and Medical Engineering,Beihang University,Beijing 100083,China)

机构地区：[1]北京航空航天大学生物与医学工程学院,生物力学与力学生物学教育部重点实验室,北京市生物医学工程高精尖创新中心,北京100083

出　　处：《医用生物力学》2023年第1期149-155,163,共8页Journal of Medical Biomechanics

基　　金：国家自然科学基金项目(11827803,11421202,11302020)。

摘　　要：目的 研究周期性牵张应变对大鼠骨髓间充质干细胞(rat bone marrow-derived mesenchymal stem cells,rBMSCs)向神经细胞分化的影响。方法 对rBMSCs加载不同幅度周期性应变24 h,然后继续培养5 d,检测神经细胞标志物表达和相关信号通路蛋白磷酸化水平。通过有限元分析牵张作用下细胞表面的应力分布。通过转录组测序分析周期性牵张应变引起差异表达的基因。结果 5%幅度、0.5 Hz周期性牵张应变可以显著促进神经细胞标志物的表达,提高细胞内胞外信号调节激酶(extracellular-signal-regulated kinase,ERK)、蛋白激酶B (AKT)和哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)的磷酸化水平。KEGG通路富集分析发现,与细胞黏附、细胞外基质和受体相互作用相关的基因在周期性牵张作用后显著提高。结论 周期性牵张应变可以改变细胞与细胞外基质的相互作用,激活AKT/mTOR和ERK信号通路,从而促进rBMSCs向神经细胞分化。了解力学刺激对间充质干细胞分化的影响有望提高干细胞向神经细胞分化的效率,有利于组织工程的装置设计,促进间充质干细胞在神经组织再生和修复的临床应用。Objective To study the mechanical effects of cyclic strain on neural differentiation of rat bone marrow mesenchymal stem cells(rBMSCs).Methods The rBMSCs were subjected to cyclic strain for 24 hours and then cultured for 5 days.The expression of neural markers and the phosphorylation of relative signaling pathway proteins were evaluated.The stress distribution on cell surface was analyzed by finite element method.The differentially expressed genes induced by strain were identified by RNA sequencing analysis.Results The 0.5 Hz strain with 5% magnitude could significantly induce higher expression of neural markers and elevated phosphorylation level of extracellular-signal-regulated kinase(ERK),protein kinase B(AKT) and mammalian target of rapamycin(mTOR).KEGG pathway analysis showed that the focal adhesion and ECM-receptor interaction were significantly enriched under cyclic strain.Conclusions Cyclic strain could change the interaction of cells with the extracellular matrix(ECM) and enhance the AKT/mTOR and ERK pathway,finally promote rBMSC neural differentiation.Knowledge about the impact of mechanical stimulation on BMSC neural differentiation is expected to improve the efficiency of stem cell differentiation,shed light on device design for tissue engineering,and promote clinical application of mesenchymal stem cells in neural issue repair and regeneration.

关 键 词：周期性牵张 骨髓间充质干细胞 神经细胞 细胞分化 

分 类 号：R318.01[医药卫生—生物医学工程]