SIRT1在老年骨髓间充质干细胞抗衰老和功能优化中的作用及机制研究

项目名称： SIRT1在老年骨髓间充质干细胞抗衰老和功能优化中的作用及机制研究

项目编号： No.31201101

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 发育生物学与生殖生物学

项目作者： 刘先宝

作者单位： 浙江大学

项目金额： 24万元

中文摘要： 骨髓间充质干细胞（MSCs）移植是缺血性心肌病最具潜力的治疗方法，但是如何提高其移植疗效是研究的热点和瓶颈问题。研究证实，来自年老个体的MSCs发生衰老并在分化、自我更新和血管新生等能力上远不如来自年轻个体的细胞，这是目前临床试验中心功能改善不明显的重要原因。因此，如何抗老年MSCs衰老并改善其功能是提高移植疗效的关键。我们的前期研究发现，老年MSCs的衰老、自我更新能力差与SIRT1的表达降低有关，SIRT1激活剂Resveratrol能够逆转老年MSCs的衰老和生长缓慢现象，因此我们推测SIRT1在老年MSCs抗衰老和功能优化中起重要作用。本研究应用基因高表达、shRNA、小动物超声、MicroPET等先进的研究手段，结合体外、体内实验对SIRT1在老年MSCs抗衰老以及功能优化中的作用及其机理进行深入的研究，为提高老年人群MSCs自体移植治疗缺血性心肌病提供一种新的思路和实验依据。

中文关键词： 骨髓间充质干细胞；衰老；SIRT1；TPP1；心肌梗死

英文摘要： Mesenchymal stem cells (MSCs) are very promising for the treatment of ischemic heart diseases, but how to improve the outcome is the highlight and bottleneck in this field. It has been confirmed that the capacities of differentiation, self-renewal and angiogenesis decreased in MSCs from elderly individuals (old MSCs). And this is one of the most important issues why MSCs have no ideal therapeutic effects on the ischemic heart diseases. Therefore, how to prevent senescence, even rejuvenize, and enhance the function of old MSCs is the key point to improve the efficacy of MSCs transplantation. Our previous studies found that senescence and lower self-renewal of old MSCs were related to the decreased expression of SIRT1 which can be partially reversed by SIRT1 activation reagent, Resveratrol. Thus, we hypothesize that SIRT1 will exert beneficial effects of anti-senescence and function improvent on old MSCs. In this study, we will evaluate the effects of SIRT1 on anit-senescence and function improvement of old MSCs, in vitro and in vivo, by using gene over-expression, shRNA, small animal echo, MicroPET, etc. We would like to explore a new method to improve the therapeutic efficacy of MSCs from old individuals.

英文关键词： mwsenchymal stem cell；age；SIRT1；TPP1；myocardial infarction