应用生物工程骨髓干细胞移植治疗房室传导阻滞的实验研究

The treatment for bradyarrhythmia is to install permanent pacemaker, but there are many defects. Reconstructing the atrioventricular conduction pathway and recovering the cardiac conduction function by application of biological tissue engineering to replace the electronic pacemaker is the direction of future development. This project is that the biological tissue engineering transplantation organization was made of self-assembling peptide nanofiber hydrogel (SAPNH), genetically modified bone marrow mesenchymal stem cells and silicon tube mould. The electrical physiological characteristics such as electrical conduction function, ion channels and cell gap junction of biological tissue engineering transplantation organization were researched, a single stem cell excitability and conductivity were evaluate by cellular electrophysiology technology in vitro. Ultimate goal of this project is to restore atrioventricular conduction function by means of biological engineering organization. This project is to establish the method of treatment for bradyarrhythmia by means of biological interventional technique, is a innovation for the treatment of bradyarrhythmia applying biological engineering organization and stem cell technology, has important scientific significance, the international advanced level and clinical practical value.

缓慢性心律失常的治疗是安装永久起搏器，但存在许多缺陷。应用生物组织工程技术构建房室传导路，重建心脏房室传导功能，以取代电子起搏器是未来发展的方向。本项目以自组装肽纳米纤维水胶为支架，将骨髓间叶干细胞、基质胶制备生物组织工程移植体，应用细胞电生理技术，观察生物工程组织的电传导功能、细胞离子通道以及缝隙连接等电生理特性。最终目的为应用生物工程组织重建房室传导功能。本项目从生物介入角度治疗缓慢型心律失常，是生物工程组织与干细胞高新技术在心律失常治疗思路的一个创新，具有重要科学意义、国际先进水平和临床实用价值。

本课题已成功进行犬骨髓间叶干细胞的分离、培养、鉴定、扩增。已成功应用自组装肽纳米纤维水胶制备组织工程移植物载体，直径2mm，长度5mm。并将分化的干细胞种植于组织工程载体上，继续培养分化成功。分离组织工程载体的分化的骨髓干细胞，应用膜片钳技术检测干细胞动作电位，证实干细具备电兴奋和传导功能。应用电镜、免疫组化技术观察组织工程移植体上的骨髓干细胞之间具备缝隙连接功能，包括表达Cx43，Cx40。表明组织工程载体具备电传导功能，可以用于实验动物房室结区的载体移植。自组装肽纳米纤维支架生物工程技术重建房室传导，可修复损伤的房室传导功能，为众多完全性房室阻滞患者提供崭新有效的生物介入治疗方法，提高患者的生存质量，具有令人兴奋的临床应用前景。