TPP1在改善老年骨髓间充质干细胞衰老和功能优化中的作用及其机制研究

骨髓间充质干细胞（MSCs）作为一种具有良好应用前景的新疗法，已在大量的临床试验中展现了确切的疗效，但其局限性也逐渐显露。老年个体来源的MSCs在细胞数量、增殖和分化能力、移植存活率、旁分泌功能、抵抗不良环境应激能力、移植治疗缺血性心脏病的效果等方面均有显著的下降。因此，年龄问题成为制约其治疗效果的关键。我们前期的研究发现，老年大鼠来源的MSCs衰老情况与端粒结合蛋白的表达水平呈负相关，而在老年来源的MSCs中过表达端粒结合蛋白关键成分TPP1可以改善其衰老表型。所以，TPP1在改善老年个体来源的MSCs功能上可能发挥着重要的作用。本研究拟通过基因过表达与干扰、荧光原位杂交、小动物超声、MicroPET等先进手段，综合体外和体内实验对TPP1在改善老年来源的MSCs衰老和疗效中的作用及其机制进行深入研究，进而为提高老年人MSCs自体移植治疗缺血性心脏病提供新的思路。

Transplantation of MSCs is a very promising therapy for myocardial infarction, which efficacy has been identified in quantity of clinical trials, but there are still some limitations in their clinical application. One of these limitations is that the MSCs used in autologous transplantation are aged population derived. According to some research, the cell number, cell proliferating and differentiation, cell engraftment, paracrine, resistance to bad environment, therapeutic efficacy of MSCs derived from aged population are all declined comparing to that of MSCs derived from young population. Our previous research have found that the senescence of aged MSCs is associated with the expression of telomere bound protein shelterin, and overexpression of TPP1, one component of the shelterin, could reverse the senescence phenotypes. Therefore, we think that TPP1 might play an important role in modifying the function of aged population derived MSCs. In this study, we will evaluate the effects of TPP1 on anit-senescence and functional optimization of aged MSCs by using gene over-expression, shRNA, FISH, small animal echo, MicroPET in vitro and in vivo. We would like to explore a new method to improve the therapeutic efficacy of MSCs from aged population.