衰老对骨髓基质干细胞刺激心肌梗死后心脏前体细胞群重建的影响及机制研究

项目名称： 衰老对骨髓基质干细胞刺激心肌梗死后心脏前体细胞群重建的影响及机制研究

项目编号： No.81200151

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 梁宏亮

作者单位： 中国人民解放军第四军医大学

项目金额： 23万元

中文摘要： 来源于衰老个体的基质干细胞（MSCs）对心肌梗死（MI）疗效下降，但机制不明。我们首先发现MSCs分泌色素上皮衍生因子(PEDF)对MI有重要调控作用，衰老MSCs高表达PEDF是其疗效下降的重要原因。PEDF是首个被证明不利于MI恢复的MSCs旁分泌信号，因此更值得关注。新近研究表明MI后心脏前体细胞群(CPCs)的重建对MI恢复至关重要。我们初步证明PEDF显著影响CPCs增殖凋亡；与年轻MSCs相比，MI后给予衰老MSCs使CPCs的数量和向心肌分化明显减少，有力提示MSCs分泌PEDF可调控CPCs微环境；衰老MSCs高分泌PEDF使MI后CPCs重建受抑制是其疗效下降的重要机制。本课题以PEDF为切入点，在分子、细胞和在体水平研究衰老MSCs对MI后CPCs重建的影响及关键分子机制，证实PEDF为靶点可提高衰老MSCs对CPCs重建的刺激作用，进而改善疗效，为MI治疗提供新思路。

中文关键词： 色素上皮衍生因子；干细胞；缺血性心脏病；；

英文摘要： The therapeutic effect of mesenchymal stem cells (MSCs) from aged donors for myocardial infarction (MI) is impaired. The underlying mechanisms remains unknown. In the previous studies, we reported that pigment epithelium derived factor (PEDF) secreted by MSCs played an important role in MI. Moreover,the up-regulated PEDF expression in aged MSCs blunted its therapeutic effects, but the mechanism is unclear. PEDF is the first identified paracrine factor of MSCs that is detrimental for the recovery of MI, which indicates its crucial role in regulating MI. It is recently reported that restitution of cardiac progenitor cells (CPCs) greatly contributed to the recovery of MI. We have demonstrated that the proliferation and apoptosis of CPCs were notably affected by PEDF; comparing with younger MSCs, transplantion of aged MSCs following MI diminished the quantity of CPCs and inhibited the differentiation of CPCs to cardiomyocytes . Therefore, we propose our hypothesis that PEDF secreted by MSCs regulates the microenvironment of CPCs. Increased PEDF level in aged MSCs hinders the restitution of CPCs. The present project is aimed to investigate the underlying molecular mechanisms of the blunted effect of aged MSCs in restituting of CPCs after MI at molecular, cellular and in vivo levels, and to certify the feasibility of

英文关键词： PEDF；stem cells；ischemic heart disease；；