Myocardium-targeted delivery of endothelial progenitor cells by ultrasound-mediated microbubble destruction improves cardiac function via an angiogenic response
Myocardium-targeted delivery of endothelial progenitor cells by ultrasound-mediated microbubble destruction improves cardiac function via an angiogenic response
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DOI：
10.1016/j.yjmcc.2006.03.012
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发表时间：
2006-06-01
影响因子：
5
通讯作者：
Matsubara, Hiroaki
中科院分区：
文献类型：
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作者：
Zen, Kan;Okigaki, Mitsuhiko;Matsubara, Hiroaki
应用超声介导的骨骼肌微泡破坏（US + Bubble）造成毛细血管破裂，导致细胞成分渗漏。我们研究了US + Bubble联合骨髓源性单核细胞（BM-MNCs）输注是否能够将内皮细胞系细胞靶向递送到心肌中，并由于缺乏新毛细血管形成而改善心肌病模型的心功能。在静脉注射微泡（option (R)）后，再输注BM-MNCs，将脉冲US应用于BIOTO2型心肌病仓鼠前胸90 s。治疗12周后，对US +微泡+ BM- mncs （US + Bubble + BM）、US + Bubble、US +无泡BM和生理盐水输注对照组的心脏样本进行分析。经US + Bubble移植的标记bm - m - nc主要定位于微血管，而未经US + Bubble刺激的标记bm - m - nc主要定位于微血管（121.2 +/- 24.5 vs. 2.80 +/- 1.30个细胞/mm， p < 0.001）。US + Bubble + BM组毛细血管密度较对照组增加1.7倍（P < 0.05），且US + Bubble和US + BM均未促进新毛细血管形成。99(m)Tc-Tetrofosmin显像显示，US + Bubble + BM组的血流灌注面积比对照组大48% （P < 0.01）。US + Bubble刺激诱导毛细血管黏附分子（VCAM-1和ICAM-1）的表达，而US + Bubble介导的BM-MNCs供应增加了心肌中VEGF和bFGF的含量。US + Bubble + BM组左心室wt/体wt、心肌纤维化面积、凋亡细胞数分别较对照组显著降低82%、73%、64% （P < 0.05）。US + Bubble + BM治疗后，肌病仓鼠心功能明显改善36% （P < 0.05）。US + Bubble将BM-N/ fnc靶向递送至心肌病仓鼠心肌，可增加毛细血管密度和局部血流量，抑制心脏重构，预防心衰。这种无创细胞输送系统可能是一种新的有效的心肌血管生成细胞治疗方法。(c) 2006爱思唯尔公司版权所有。
Application of ultrasound-mediated destruction of microbubbles (US + Bubble) to skeletal muscle creates capillary ruptures leading to leakage of the cell components. We studied whether US + Bubble combined with bone-marrow-derived mononuclear cells (BM-MNCs) infusion enables the targeted delivery of endothetial-lineage cells into the myocardium and improves cardiac function of the cardiomyopathy model due to the paucity of neocapillary formation. Pulsed US was applied to the anterior chest of BIOTO2 cardiomyopathy hamsters for 90 s after the intravenous injection of microbubble (Optison(R)) followed by infusion of BM-MNCs. Cardiac samples from US + microbubble + BM-MNCs (US + Bubble + BM), US + Bubble, US + BM without Bubble, and saline infusion control groups were analyzed 12 weeks after treatment. Labeled BM-M-NCs transplanted by US + Bubble were found to be mainly localized in the microvessels, but not by US stimulation without microbubble (121.2 +/- 24.5 vs. 2.80 +/- 1.30 cells/mm(2), p < 0.001). Capillary densities in US + Bubble + BM group were increased 1.7-fold (P < 0.05) over the control, and neither US + Bubble nor US + BM enhanced neocapillary formation. 99(m)Tc-Tetrofosmin scintigraphy revealed that blood perfusion area in the US + Bubble + BM group was 48% greater than the control (P < 0.01). US + Bubble stimulation induces the expression of adhesion molecules (VCAM-1 and ICAM-1) in capillaries, and the US + Bubble-mediated supply of BM-MNCs increased the myocardial content of VEGF and bFGF. The left ventricular wt/body wt, area of cardiac fibrosis, and apoptotic cell numbers in the US + Bubble + BM group significantly (P < 0.05) decreased by 82%, 73%, and 64% relative to the control, respectively. The cardiac function in myopathic hamsters (assessed by fractional shortening) was markedly improved 36% (P < 0.05) by US + Bubble + BM treatment. Targeted delivery of BM-N/fNCs by US + Bubble to the myocardium of the cardiomyopathic hamster increased the capillary densities and regional blood flow and inhibited cardiac remodeling, resulting in the prevention of heart failure. This noninvasive cell delivery system may be useful as a novel efficient approach for angiogenic cell therapy to the myocardium. (c) 2006 Elsevier Inc. All rights reserved.