心脏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，已成功将HCN4基因转染至犬骨髓间充质干细胞(MSCs)，并在体外诱导培养出心脏起搏样细胞；通过将HCN4基因修饰的MSCs移植至犬心室肌重建生物起搏点获得成功，但因起搏频率较体外培养的细胞搏动频率明显减慢，成为制约该项研究的关键问题。研究显示，Shox2、Nkx2.5及Tbx3均是与心脏胚胎发育密切相关的转录调控因子，其中Shox2基因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，本项目研究拟在体外先将Shox2基因导入经HCN4基因修饰的MSCs，再将其移植至窦房结毁损犬右心房外膜下，重建出起搏频率及持续时间均较理想的心脏生物起搏点。本研究成果将有助于提升心脏生物起搏研究的应用价值，促进生物起搏治疗缓慢性心律失常的临床应用进程。具有重要的理论意义与潜在的临床实用价值。

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 pace maker can be detected when these MSCs 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 Shox2、Nkx2.5 and Tbx3 were closely related to the heart prenatal development and Shox2 especially 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 a ideal pace maker with better pacing frequency and persistence time, we are gonging to transfect Shox2 gene to those MSCs which has already been transfected with HCN4 gene before transplanting them to right atrium where the sinoatrial node has been destroyed. The work will improve the study of biological pacemaker and facilitated its clinical application, which will make great theory value as well as potential clinical practice.