胚胎干细胞来源的AT2受体阳性细胞修复心肌损伤及其心肌分化机制研究

Despite many studies show that stem cells transplantiation can repair myocardial injury caursed by ischemia,the source of adult cardiac stem cells is limited due to amplification issues. Embryonic stem cells(ESCs) possess the ability of self-renewal and are able to maintain their pluripotent potential. This allows the possibility of ESCs to be used in cell therapy and tissue repairing. Although some studies indicate the existence of cardiovascular progenitor cells in ESCs, only mixed cell populations obtained so far safety issue still exist. Angiotensin 2 (AT2) receptor mediates the down-regulation of excessive proliferation. AT2 receptor activation contributing to cardioprotection through modulating cell differentiation and regeneration during tissue injury/repair events. Lack of AT2 receptor infect the postnatal cardiovascular development and muturation of mouse. Our previous studies show that cardiac c-kit+AT2R+ cell population increases after acute ischemic injury. Interestingly, we further detected that almost concurrent AT2 receptor expression along with the derivation of myocardium differentiation. The aim of our study is to investigate the circuit between AT2 receptor expression and myocardium differentiation by using mouse ES cell lines. Therefore, we are using a new innovative method for the enrichment of myocardiac progenitor cells through the AT2 receptor in order to use these cells to repair myocardiac injury after myocardial infarction. In addition, we will also focus on modulatory mechanisms of myocardial differentiation in ESCs.Taken together, our study shall provide new insights of using ESCs transplantation for heart injury repair.

研究显示干细胞移植可改善心肌修复。成体来源的心脏干细胞来源有限且无法大量扩增。胚胎干细胞（ESCs）具有强大的增殖和分化潜能。研究报道ESCs中存在心血管前体细胞，但大部分研究只能分离获得混杂的细胞群。有研究显示AT2受体(血管紧张素II受体II型)可以调控细胞的增殖和分化。AT2R缺失会影响鼠心脏发育和成熟。我们前期研究显示，心肌损伤发生后，骨髓及心脏c-kit+AT2R+细胞数量及迁移能力增加，提示AT2R在心肌细胞分化和组织再生修复过程起着重要的作用。我们前期在小鼠胚胎干细胞系中发现，AT2R表达时间与心肌分化起始时间相一致。基于以上研究背景，我们拟从小鼠ESCs出发，研究AT2R表达与心肌分化潜能的关系，试图通过AT2R从ESCs中富集到心肌前体细胞。并利用这群细胞修复小鼠缺血性心肌损伤。同时对AT2R调控心肌分化的机制进行研究，为胚胎干细胞心肌损伤修复应用的可能性提供理论依据。