Intracoronary delivery of umbilical cord blood derived unrestricted somatic stem cells is not suitable to improve LV function after myocardial infarction in swine
Intracoronary delivery of umbilical cord blood derived unrestricted somatic stem cells is not suitable to improve LV function after myocardial infarction in swine
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DOI：
10.1016/j.yjmcc.2007.01.005
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发表时间：
2007-04-01
影响因子：
5
通讯作者：
van der Giessen, Wirn J.
中科院分区：
文献类型：
--
作者：
Moelker, Amber D.;Baks, Timo;van der Giessen, Wirn J.
通过注射干细胞再生梗死心肌可以预防心力衰竭。我们研究了ICC。人脐血干细胞(USSC)在猪心肌梗死(MI)和再灌注模型中的应用15只猪采用冠状动脉左回旋支(LCX)球囊结扎2 h后再灌流的方法复制MI模型。5头猪作为健康对照。1周后行磁共振成像(MRI)评价左心功能和梗塞面积。然后，在免疫抑制的情况下，存活的12头MI猪中的6头接受冠状动脉内注射类似于10(8)人USSC的LCX，而另一头MI猪接受中等剂量的USSC。四周后，所有的猪都接受了MRI的随访，并被处死做组织学检查。心肌梗死后1周，舒张末容量(92+/-3m L)和左心室重量(75+/-2g)大于正常对照组(68+/-3m L，66+/-3g和55+/-3%，P均<0.05)，射血分数(42+/-2%)小于健康对照组(68+/-3m L，66+/-3g和55+/-3%，P均<0.05)。Lcx区节段性室壁增厚(-7+/-2%)基本消失。在5周时，接受USSC和中等剂量组的MI动物的整体和局部左心功能没有差异。USSC治疗后梗塞面积显著增大(20+/-3g比8+/-2g，P<；0.05)。USSC在5周后仅存活于梗死区，且不表达心肌细胞或内皮细胞标志物。组织学显示，冠状动脉内注射USSC可通过阻塞血管而导致微小梗塞。在1周龄心肌梗死的猪中，4周后经冠状动脉内注射USSC并不能改善左心功能。(C)2007 Elsevier Inc.保留所有权利。
Regeneration of infarcted myocardium by injecting stem cells has been proposed to prevent heart failure. We studied the i.c. administration of human umbilical cord blood stem cells (USSC) in a porcine model of myocardial infarction (MI) and reperfusion. In 15 swine, MI was induced by balloon-occlusion of the left circumflex coronary artery (LCX) for 2 h followed by reperfusion. Five swine served as healthy controls. One week later, magnetic resonance imaging (MRI) was performed to assess left ventricular (LV) function and infarct size. Then, under immune suppression, 6 of the 12 surviving MI swine received intracoronary injection of similar to 10(8) human USSC in the LCX while the other MI-swine received medium. Four weeks later all swine underwent follow-up MRI, and were sacrificed for histology. One week after MI, end-diastolic volume (92 +/- 3 mL) and LV mass (75 +/- 2 g) were larger, while ejection fraction (42 +/- 2%) was smaller than in healthy control (68 +/- 3 mL, 66 +/- 3 g and 55 +/- 3%, all P < 0.05). Regional wall thickening (-7 +/- 2%) in the LCX area became akinetic. No difference in global and regional LV function at 5 weeks was observed between MI animals receiving USSC or medium. Infarct size after USSC treatment was significantly larger (20 +/- 3 g vs. 8 +/- 2 g, P < 0.05). USSC survived only in the infarct border zone at 5 weeks and did not express cardiomyocyte or endothelial markers. Histology showed that intracoronary injection of USSC caused micro infarctions by obstructing blood vessels. In swine with a 1 week old MI, injection of USSC via the intracoronary route does not improve LV function 4 weeks later. (c) 2007 Elsevier Inc. All rights reserved.