Wolf David, Reinhard Adrian, Krause Ulf, Seckinger Anja, Katus Hugo A, Kuecherer Helmut, Hansen Alexander
Department of Cardiology and Angiology, University of Heidelberg, Heidelberg, Germany.
J Am Soc Echocardiogr. 2007 May;20(5):512-20. doi: 10.1016/j.echo.2006.11.008.
Intravenous delivery of mesenchymal stem cell (MSC) is a noninvasive approach for myocardial tissue repair. We aimed to test this strategy in a pig model of myocardial infarction and to examine the usefulness of new echocardiographic applications to monitor cardioprotective effects of stem cell therapy.
Pigs (n = 8) received autologous or allogeneic MSCs (1 x 10(6)/kg body weight) labeled with fluorescent dye 48 hours after proximal left anterior descending coronary artery occlusion. Infarct size, myocardial function, and perfusion (A x beta) were assessed by myocardial contrast echocardiography and standard histologic methods after 1 month.
Morphologic analysis revealed that labeled MSCs migrated in the peri-infarct region resulting in smaller infarct size by myocardial contrast echocardiography (control vs autologous and allogeneic MSC: 38 +/- 10% vs 25 +/- 5% and 28 +/- 6%, P < .01), higher fractional area shortening (23 +/- 3% vs 34.0 +/- 7% and 28 +/- 2%, P < .01), higher cardiac synchrony (167 +/- 36 vs 68 +/- 17 and 85 +/- 26 milliseconds, P < .003), and improved microvascular flow A x beta in the ischemic border zone (0.18 +/- 0.2 vs 0.56 +/- 0.3 and 0.49 +/- 0.2, P < .03).
Systemic delivery of autologous and allogeneic MSCs preserves myocardial viability even in large animals and is, therefore, an attractive approach for tissue repair. Myocardial contrast echocardiography is useful to evaluate microvascular perfusion, which was enhanced by MSCs.
静脉输注间充质干细胞(MSC)是一种用于心肌组织修复的非侵入性方法。我们旨在在猪心肌梗死模型中测试该策略,并研究新型超声心动图应用在监测干细胞治疗心脏保护作用方面的实用性。
猪(n = 8)在左前降支冠状动脉近端闭塞48小时后接受自体或异体MSC(1×10⁶/千克体重),并用荧光染料标记。1个月后,通过心肌对比超声心动图和标准组织学方法评估梗死面积、心肌功能和灌注(A×β)。
形态学分析显示,标记的MSC迁移至梗死周边区域,通过心肌对比超声心动图观察到梗死面积减小(对照组与自体和异体MSC组:38±10% 对 25±5% 和 28±6%,P <.01),缩短分数增加(23±3% 对 34.0±7% 和 28±2%,P <.01),心脏同步性提高(167±36对68±17和85±26毫秒,P <.003),缺血边缘区微血管血流A×β改善(0.18±0.2对0.56±0.3和0.49±0.2,P <.03)。
自体和异体MSC的全身递送即使在大型动物中也能保留心肌活力,因此是一种有吸引力的组织修复方法。心肌对比超声心动图有助于评估微血管灌注,MSC可增强微血管灌注。