Intracoronary delivery of autologous cardiac stem cells improves cardiac function in a porcine model of chronic ischemic cardiomyopathy.
Intracoronary delivery of autologous cardiac stem cells improves cardiac function in a porcine model of chronic ischemic cardiomyopathy.
复制标题
DOI：
10.1161/circulationaha.112.001075
复制
发表时间：
2013-07-09
期刊：
影响因子：
37.8
通讯作者：
Kajstura J
中科院分区：
文献类型：
--
作者：
Bolli R;Tang XL;Sanganalmath SK;Rimoldi O;Mosna F;Abdel-Latif A;Jneid H;Rota M;Leri A;Kajstura J
相关的临床前模型对于c-kit+心脏干细胞（CSCs）的进一步机制和转化研究是必要的。本研究旨在确定冠状动脉内CSC是否对慢性缺血性心肌病猪模型有益。猪进行了90分钟的冠状动脉闭塞，然后再灌注。三个月后，将自体CSC（n=11）或载体（n=10）输注到梗死相关动脉中。此时，对照组和CSC治疗组的所有LV功能指标相似，表明两组中梗死造成的损害相似;然而，一个月后，CSC治疗的猪表现出显著更高的LV射血分数（超声心动图）（51.7 ± 2.0% vs.42.9 ± 2.3%，P<0.01），梗死左室壁收缩期增厚分数，最大左室dP/dt，以及较低的LVEDP。共聚焦显微镜显示，在处理猪的瘢痕中存在表达Ki 67的小α-肌节肌动蛋白阳性细胞簇，与心脏再生一致。这些来自注射细胞的循环肌细胞的起源在接受EGFP标记的CSC的四只猪中得到证实，这些CSC对心脏标志物肌钙蛋白I、肌钙蛋白T、肌球蛋白重链和连接蛋白-43呈阳性。一些移植的CSC还形成血管结构并表达α-平滑肌肌动蛋白。冠状动脉内输注自体CSC可改善陈旧性MI（瘢痕）猪的局部和整体LV功能，并促进心脏和血管再生。结果模拟了最近在人类中报道的结果（SCIPIO试验），并建立了这种缺血性心肌病的猪模型，作为研究CSC的有用和临床相关模型。
Relevant preclinical models are necessary for further mechanistic and translational studies of c-kit+ cardiac stem cells (CSCs). The present study was undertaken to determine whether intracoronary CSCs are beneficial in a porcine model of chronic ischemic cardiomyopathy. Pigs underwent a 90-min coronary occlusion followed by reperfusion. Three months later, autologous CSCs (n=11) or vehicle (n=10) were infused into the infarct-related artery. At this time, all indices of LV function were similar in control and CSC-treated pigs, indicating that the damage inflicted by the infarct in the two groups was similar; one month later, however, CSC-treated pigs exhibited significantly greater LV ejection fraction (echocardiography) (51.7 ± 2.0% vs. 42.9 ± 2.3 %, P<0.01), systolic thickening fraction in the infarcted LV wall, and max LV dP/dt, as well as lower LVEDP. Confocal microscopy showed clusters of small α-sarcomeric actin positive cells expressing Ki67 in the scar of treated pigs, consistent with cardiac regeneration. The origin of these cycling myocytes from the injected cells was confirmed in four pigs that received EGFP-labeled CSCs, which were positive for the cardiac markers troponin I, troponin T, myosin heavy chain, and connexin-43. Some engrafted CSCs also formed vascular structures and expressed α-smooth muscle actin. Intracoronary infusion of autologous CSCs improves regional and global LV function and promotes cardiac and vascular regeneration in pigs with old MI (scar). The results mimic those recently reported in humans (SCIPIO trial) and establish this porcine model of ischemic cardiomyopathy as a useful and clinically-relevant model for studying CSCs.