心脏生物起搏是心电生理领域研究的重点之一。本课题组前期研究及国内外同类研究均显示，经HCN4基因修饰的MSCs在体外可分化为心脏起搏样细胞，将经HCN4基因修饰的MSCs移植至Ⅲº房室传导阻滞动物心室肌可重建心脏生物起搏点，但其频率较培养获得的心脏起搏样细胞搏动频率明显减慢，不能满足生物起搏功能需要。本项目通过对生物起搏功能低下的可能原因进行分析，提出了GJA7与HCN4双基因转染骨髓源性心脏干细胞（MCSCs）移植、提高生物起搏频率的新策略，并用水凝胶运载移植细胞、用SPIO标记细胞行MRI活体示踪观察等方法。其目的旨在提高移植细胞Cx45表达、促进移植细胞与宿主细胞间电-机械偶联的建立，防止移植细胞“流失”，使移植细胞在宿主体内长期存活并有效分化为心脏起搏样细胞，建立具有稳定、高效起搏功能的生物起搏点。本研究结果将为心脏生物起搏治疗缓慢性心律失常临床前研究奠定实验基础，具有重要意义。

Biological pacemaker therapy has been a hot spot and emphasis of cardiac electrophysiology study in recent years. With the help of national natural science foundation we have successfully cultivated pacing cells derived from MSCs transfected with HCN4 gene in vitro. A biological pacemaker can be detected when these MSCs were transplanted to the ventricular muscle, but the pacing rate was much lower than the normal sinus rhythm. It may be the result of insufficient survival pacemaker-like cells and deficient electromechanical coupling with cardiomyocytes. Researches have demonstrated that gap junction protein Cx45 uniquely express in sinus node (SAN) and plays a key role in the electrophysiological properties of SAN. In order to establish an ideal pacemaker with better pacing frequency and persistence time, we set out to co-transfect GJA7 and HCN4 in canine marrow derived cardiac stem cells, and transplant them to the region where the atrioventricular node has been destroyed through self-assembling peptide scaffolds. Then we are going to monitor the trace of these transplanted cells within body through SPIO by MRI. This work will improve the study of biological pacemaker and facilitated its clinical application, which will make greater theory value as well as potential clinical practice.