Department of Cardiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Ultrasound Med Biol. 2013 Nov;39(11):2001-10. doi: 10.1016/j.ultrasmedbio.2013.06.003. Epub 2013 Aug 19.
The myocardial microenvironment plays a decisive role in the survival, migration and differentiation of stem cells. We studied myocardial micro-environmental changes induced by ultrasound-targeted microbubble destruction (UTMD) and their influence on the transplantation of mesenchymal stem cells (MSCs). Various intensities of ultrasound were applied to the anterior chest in canines with myocardial infarction after intravenous injection of microbubbles. The expression of cytokines and adhesion molecules in the infarcted area of the myocardium was detected after three sessions of UTMD in 1 wk. Real-time quantitative reverse transcription polymerase chain reaction (RTQ-PCR) showed that the expression of vascular cell adhesion molecule-1 (VCAM-1), stromal cell-derived factor-1 (SDF-1) and vascular endothelial growth factor (VEGF) in the 1.5 W/cm(2) and 1 W/cm(2) groups was markedly increased compared with the 0.5 W/cm(2) or the control groups (3.8- to 4.7-fold, p < 0.01), and the expression of interleukin-1β (IL-1β) in the 1.5 W/cm(2) group was increased twofold over the 1.0 W/cm(2) group, whereas the 0.5 W/cm(2) group experienced no significant changes. UTMD at 1.0 W/cm(2) was performed as previously described before mesenchymal stem cell (MSC) transplantation. Myocardial perfusion, angiogenesis and heart function were investigated before and 1 month after MSC transplantation. Coronary angiography and 99mTc-tetrofosmin scintigraphy revealed that myocardial perfusion was markedly improved after UTMD + MSCs treatment (p < 0.05). At echocardiographic analysis, heart function and the wall motion score index were significantly improved by UTMD + MSCs treatment compared with MSCs or UTMD alone and the control. In a canine model of myocardial infarction, therapeutic effects were markedly enhanced by MSC transplantation after the myocardial micro-environmental changes induced by UTMD; therefore, this novel method may be useful as an efficient approach for cellular therapy.
心肌的微环境在干细胞的存活、迁移和分化中起着决定性的作用。我们研究了超声靶向微泡破坏（UTMD）诱导的心肌微环境变化及其对间充质干细胞（MSCs）移植的影响。在犬心肌梗死后，通过静脉注射微泡，在其前胸部施加不同强度的超声。在第 1 周进行 3 次 UTMD 后，检测心肌梗死区细胞因子和黏附分子的表达。实时定量逆转录聚合酶链反应（RTQ-PCR）显示，1.5W/cm(2)和 1W/cm(2)组血管细胞黏附分子-1（VCAM-1）、基质细胞衍生因子-1（SDF-1）和血管内皮生长因子（VEGF）的表达明显高于 0.5W/cm(2)或对照组（3.8-4.7 倍，p<0.01），1.5W/cm(2)组白细胞介素-1β（IL-1β）的表达是 1.0W/cm(2)组的两倍，而 0.5W/cm(2)组无明显变化。在 MSC 移植前，按先前的描述进行 1.0W/cm(2)UTMD。在 MSC 移植前和移植后 1 个月，进行心肌灌注、血管生成和心功能的检测。冠状动脉造影和 99mTc-四氮脒闪烁扫描显示，UTMD+MSCs 治疗后心肌灌注明显改善（p<0.05）。在超声心动图分析中，UTMD+MSCs 治疗组的心功能和壁运动评分指数明显优于 MSC 组或 UTMD 组和对照组。在犬心肌梗死模型中，UTMD 诱导的心肌微环境变化后 MSC 移植可显著增强治疗效果；因此，这种新方法可能是细胞治疗的有效方法。
