Transplantation of SIRT1-engineered aged mesenchymal stem cells improves cardiac function in a rat myocardial infarction model
Transplantation of SIRT1-engineered aged mesenchymal stem cells improves cardiac function in a rat myocardial infarction model
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SIRT1 工程改造的老化间充质干细胞移植可改善大鼠心肌梗死模型的心脏功能
DOI：
10.1016/j.healun.2014.05.008
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发表时间：
2014-10-01
影响因子：
8.9
通讯作者：
Wang, Jian'an
中科院分区：
文献类型：
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作者：
Liu, Xianbao;Chen, Huiqiang;Wang, Jian'an
背景技术背景：以往的研究表明，生物老化对间充质干细胞（MSCs）为基础的治疗效果有负面影响。使用大鼠心肌梗死（MI）模型，我们验证了沉默交配型信息调节2同源物1（SIRT 1）可以改善老年MSCs的表型和功能，从而提高老年MSCs治疗的疗效的假设。心肌内注射细胞培养基（DMEM组）;从老年雄性SD大鼠获得的SIRT 1过表达载体处理的老年MSC（SIRT 1老年MSC组）或空载体处理的老年MSC（载体老年MSC组）。另20只假手术大鼠，接受开胸手术，没有冠状动脉结扎或任何其他干预作为controls.RESULTS：SIRT 1岁的MSC组表现出增强的血管密度在边界区的MI心脏，这是与减少心脏重构，导致改善心脏性能。与体内数据一致，我们的体外实验还证明SIRT 1过表达改善了衰老MSC的衰老表型，并重现了MSC的促血管生成特性，并赋予了抗应激反应能力，如促血管生成因子血管生成素1（Ang 1）和碱性成纤维细胞生长因子（bFGF）的增加所示，抗血管生成因子血小板反应蛋白-1（TBS 1）在mRNA水平表达降低，Bcl-2/Bax比值在蛋白水平升高。上调SIRT 1表达可增强基于衰老MSC的MI治疗的功效，因为其涉及衰老表型的改善，从而改善衰老MSC的生物学功能。(C)2014年国际心肺移植学会。All rights reserved.
BACKGROUND: Previous studies have demonstrated that biological aging has a negative influence on the therapeutic effects of mesenchymal stem cells (MSCs)-based therapy. Using a rat myocardial infarction (MI) model, we tested the hypothesis that silent mating type information regulation 2 homolog 1 (SIRT1) may ameliorate the phenotype and improve the function of aged MSCs and thus enhance the efficacy of aged MSCs-based therapy.METHODS: Sixty female rats underwent left anterior descending coronary artery ligation and were randomly assigned to receiving: intramyocardial injection of cell culture medium (DMEM group); SIRT1 overexpression vector-treated aged MSCs (SIRT1-aged MSCs group) obtained from aged male SD rats or empty vector-treated aged MSCs (vector-aged MSCs group). Another 20 sham-operated rats that underwent open-chest surgery without coronary ligation or any other intervention served as controls.RESULTS: SIRT1-aged MSC group exhibited enhanced blood vessel density in the border zone of MI hearts, which was associated with reduced cardiac remodeling, leading to improved cardiac performance. Consistent with the in vivo data, our in vitro experiments also demonstrated that SIRT1 overexpression ameliorated aged MSCs senescent phenotype and recapitulated the pro-angiogenesis property of MSCs and conferred the anti-stress response capabilities, as indicated by increases in pro-angiogenic factors, angiopoietin 1 (Ang1) and basic fibroblast growth factor (bFGF), expressions and a decrease in anti-angiogenic factor thrombospondin-1 (TBS1) at mRNA levels, and increases in Bcl-2/Bax ratio at protein level.CONCLUSIONS: Up-regulating SIRT1 expression could enhance the efficacy of aged MSCs-based therapy for MI as it relates to the amelioration of senescent phenotype and hence improved biological function of aged MSCs. (C) 2014 International Society for Heart and Lung Transplantation. All rights reserved.