注射自体内皮祖细胞促进左心耳封堵术后封堵器表面内皮化的机制研究

The patient with atrial fibrillation has a higher risk of the stroke. Left atrial appendage closure (LAAC) has been developed as a minimally invasive strategy for stroke prevention in AF patienst around the world. However, the huge exposed surface of LAA occluder forces the adoption of high-intensitive anticoagulation drugs after the LAAC, which leads to potential bleeding risk and the uncertainty of endothelialization in the occluder’ s surface. Endothelial progenitor cell (EPC) is crucial in the procedure of surface endothelialization. Some small but pilot trials have revealed that the EPC-capture stent had a relatively short period of endothelialization. However, the benefit of EPC in the clinical practice was still limited as the rare of quantity in the circulatory system. .In this pilot study, the circulatory EPCs of experimental dogs would be extracted from peripheral blood, amplificated and identified in vitro. LAAC would been applied with an optimized LAA occluder. Immediately, the autologous EPC which was amplificated in vitro would be injected through the occluder’s sheath to the its surface directly for regional enrichment of EPC in the target area. At the periods of early, mid-term and long-term phases after the procedure, the endothelialization was explored through gross specimen and electron microscope observations. For potential mechanisms of endothelialization promotion, the potential roles of injected EPC adhesion and differentiation, endothelial cells proliferation, pericytes recruitment, micro-angiogenesis as well as vascular factors produce would be explored. As the hypothesis, this study might supply some potential clinical benefit for shortening the duration of anticoagulation secondart to the injection of EPCs after the LAAC.

房颤患者发生卒中的风险较高。左心耳封堵术（LAAC）是近年来广泛采用的微创封堵左心耳来预防房颤卒中的新技术。然而，术后封堵器裸露面积大，需要高强度抗凝，带来出血隐患的同时内皮化也不确定。内皮祖细胞(EPC) 在内皮化的关键，在一些小的前沿性的临床研究中发现EPC捕获型支架能缩短术后内皮化过程。但循环EPC的缺少，限制了它的临床应用。.本课题拟在LAAC术前先提取实验犬外周血循环EPC，体外培养和扩增。LAAC术后即刻通过鞘管向封堵器表面靶向注射自体EPC，提高其在需要内皮化区域的富集。观测术后早期、中期及较长期封堵器表面内皮化进程。采用大体标本、电子显微镜等手段探索封堵器表面内皮覆盖，同时探索EPC在封堵器表面的定植分化、内皮细胞增殖、周围细胞动员、微血管生成及促血管因子生成等作用。本课题将期望通过注射EPC促进LAAC后封堵器表面内皮化，为临床减少抗凝药物使用时间提供参考。

房颤患者发生卒中的风险较高。左心耳封堵术（LAAC）是近年来广泛采用的微创封堵左心耳来预防房颤卒中的新技术。然而，术后封堵器裸露面积大，需要高强度抗凝，带来出血隐患的同时内皮化也不确定。内皮祖细胞(EPC) 是内皮化的关键之一。.本课题拟研发一种内皮友好型新型左心耳封堵器并在LAAC术中即刻注射自体EPC来促进实验犬在LAAC术后的封堵器表面内皮化。目前本课题已经完成该新型左心耳封堵器的研发、专利转化及上市前多中心临床研究，随访结果显示了封堵器的临床效果好，内皮化良好。同时，大动物研究发现LAAC术中即刻注射EPC未促进实验犬在LAAC术后的封堵器表面内皮化。本研究正在使用内皮细胞进一步研究促进内皮化的机制。.本课题相关封堵器上市后将惠及广大房颤患者，凸显中国制造的优势。