Sinus node dysfunction and high-degree heart block are the major causes for electronic pacemaker implantation. Recently, genetically modified mesenchymal stromal cells (MSCs, also known as "mesenchymal stem cells") were demonstrated to generate pacemaker function in vivo. However, experimental approaches typically use open thoracotomy for direct cell injection into the myocardium. Future clinical implementation, however, essentially requires development of more gentle methods to precisely and efficiently apply specified stem cells at specific cardiac locations. In a "proof of concept" study, we performed selective power-controlled radiofrequency catheter ablation (RFCA) with eight ablation pulses (30 W, 60 seconds each) to induce heat-mediated lesions at the auricles of the cardiac right atrium of four healthy foxhounds. The next day, allogeneic MSCs (4.3 x 10(5) cells per kilogram of body weight) labeled with superparamagnetic iron oxide particles (SPIOs) were infused intravenously. Hearts were explanted 8 days later. High numbers of SPIO-labeled cells were identified in areas surrounding the RFCA-induced lesions by Prussian blue staining. Antibody staining revealed SPIO-labeled cells being positive for the typical MSC surface antigen CD44. In contrast, low levels of calprotectin, an antigen found on monocytes and macrophages, indicated negligible infiltration of monocytes in MSC-positive areas. Thus, RFCA allows targeting of MSCs to the cardiac right atrium, adjacent to the sinoatrial node, providing an opportunity to rescue or generate pacemaker function without open thoracotomy and direct injection of MSCs. This method presents a new strategy for cardiac stem cell application leading to an efficient guidance of MSCs into the myocardium. Disclosure of potential conflicts of interest is found at the end of this article.

译文

窦房结功能障碍和高度心脏传导阻滞是植入电子起搏器的主要原因。最近,转基因间充质基质细胞 (MSCs,也称为 “间充质干细胞”) 被证明在体内具有起搏器功能。然而,实验方法通常使用开胸切开术直接将细胞注射到心肌中。然而,未来的临床实施基本上需要开发更温和的方法,以便在特定的心脏位置精确有效地应用特定的干细胞。在一项 “概念验证” 研究中,我们用八个消融脉冲 (30 W,每个60秒) 进行了选择性功率控制的射频导管消融 (RFCA),以在四个心脏右心房的耳廓处诱导热介导的病变健康猎狐犬。第二天,静脉内注入用超顺磁性氧化铁颗粒 (SPIOs) 标记的同种异体msc (每千克体重4.3 × 10(5) 个细胞)。心脏在8天后被移出。通过普鲁士蓝染色,在RFCA诱导的病变周围区域中鉴定出大量SPIO标记的细胞。抗体染色显示SPIO标记的细胞对典型的MSC表面抗原cd44呈阳性。相反,钙卫蛋白 (一种在单核细胞和巨噬细胞上发现的抗原) 的水平较低,表明MSC阳性区域中单核细胞的浸润可忽略不计。因此,RFCA允许将MSCs靶向窦房结附近的心脏右心房,从而提供了挽救或产生起搏器功能的机会,而无需开胸切开术和直接注射MSCs。该方法为心脏干细胞的应用提供了一种新的策略,可有效地将MSCs引导到心肌中。在本文的末尾找到了潜在利益冲突的披露。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录