AC1基因转染iPSC来源的心肌细胞以构建生物心脏起搏器的实验研究

Electronic cardiac pacemaker is traditionally iindicated for the treatment of bradyarrhythmia. However, several defects exist for electronic pacemaker.Our research team is focusing on the construction of biological pacemaker to treat bradyarrhythmia in recent years. As a significant innovatative way, its feasibility has been varified in our previous animal experiments. The critical issue we are facing is the low frequency of biological pacing which impedes its clinical application. Our up-to-date findings proved that Ca2+-Stimulated adenylyl cyclase（CaAC）could increase the beating frequency and autonomic responsibility. Basing on the previuos work of biological pacing, we plan to transfect iPSC-derived cardiomyocyte (iPSC-CM) with AC1 which encodes CaAC by Lentivirus as vector to construct novel biological pacemaker. This project aims to improve the frequency and autonomic responsibility of biological pacing. In addition, the long-term durability will be also evaluated in this study. Footing on our early research work, we propose the creative resolution for the key issue in the building of biological pacemaker. The success of the study will efficiently promote the process of clinical applications for biological pacing.

缓慢型心律失常患者通常需要植入心脏起搏器治疗，但目前电子起搏器仍存在一定的不足。近年来本课题组致力于构建生物心脏起搏器以治疗该疾病，作为一项全新的治疗思路，其可行性已经在我们前期的动物实验中得到证实。当前存在的主要问题是生物起搏的频率较为缓慢，尚不能满足临床治疗的需要。我们的最新研究表明，钙离子刺激腺苷酸环化酶（CaAC）可以增加起搏细胞的搏动频率及其对神经递质的反应性。本项目拟在前期生物起搏研究的基础上，以慢病毒为载体，将CaAC的编码基因AC1导入诱导多能干细胞来源的心肌细胞(iPSC-CM)，以构建新型的生物心脏起搏器，从而进一步提高生物起搏的频率及其对自主神经调节的反应性。此外，我们还将对所构建的生物起搏器的远期效果进行评价。本项目立足前期研究基础，针对生物起搏研究中存在的关键问题，提出了创新性的解决方案，如获成功，将有效推动生物起搏技术的临床应用进程。