生物起搏是近年来心脏电生理领域研究的重点与热点内容之一。本课题组在国家自然科学基金资助下，使用HCN4重组慢病毒转染猪的基质干细胞，获得了稳定过表达HCN4基因、呈群体性搏动的起搏样细胞，该起搏细胞能在缓慢性心律失常模型猪体内建立有效的生物起搏点，相关研究已发表SCI论著22篇，并获得2014年度江苏省科技进步一等奖，但和国外同行的研究一样，构建的生物起搏效率偏低，这成为制约该研究的关键问题。Tbx3是与心脏胚胎发育密切相关的转录调控因子，对维持胚胎心脏起搏细胞基因表型、促进窦房结发育形成起重要调控作用。因此，本项目拟在体外将Tbx3基因导入HCN4基因转染的iPS细胞，构建新型生物起搏细胞，并将其移植至窦房结毁损猪右心房外膜下，优化重建心脏生物起搏点，建立起搏频率及持续时间均较理想的生物起搏点。本研究将有助于提升心脏生物起搏的应用价值，为构建的生物起搏细胞最终应用于临床提供理论依据。

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 stem cells transfected with HCN4 gene in vitro. A biological pacemaker can be detected when these stem cells were transplanted to the ventricular muscle, but the pacing frequency was much lower than that of in vitro which will restrict the further study on this issue. Research has demonstrated that Tbx3 is closely related to the heart prenatal development and plays an important role in the embryonic sinoatrial node development with its strict control to maintain the cytogene of sinoatrial node. In order to make an ideal pacemaker with better pacing frequency and persistence time, we are going to transfect Tbx3 gene to those iPS cells which have already been transfected with HCN4 gene before transplanting them to right atrium of swine where the sinoatrial node has been destroyed. The work will improve the study of biological pacemaker and facilitate its clinical application, which will make great theory value as well as potential clinical practice.