Center for Ultrasound Molecular Imaging and Therapeutics, Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Ultrasound Med Biol. 2012 Nov;38(11):1989-97. doi: 10.1016/j.ultrasmedbio.2012.07.019. Epub 2012 Sep 10.
Cell-based therapeutic approaches are attractive for the restoration of the protective endothelial layer in arteries affected by atherosclerosis or following angioplasty and stenting. We have recently demonstrated a novel technique for the delivery of mesenchymal stem cells (MSCs) that are surface-coated with cationic lipid microbubbles (MBs) and displaced by acoustic radiation force (ARF) to a site of arterial injury. The objective of this study was to characterize ultrasound parameters for effective acoustic-based delivery of cell therapy. In vitro experiments were performed in a vascular flow phantom where MB-tagged MSCs were delivered toward the phantom wall using ARF generated with an intravascular ultrasound catheter. The translation motion velocity and adhesion of the MB-cell complexes were analyzed. Experimental data indicated that MSC radial velocity and adhesion to the vessel phantom increased with the time-averaged ultrasound intensity up to 1.65 W/cm², after which no further significant adhesion was observed. Temperature increase from baseline near the catheter was 5.5 ± 0.8°C with this setting. Using higher time-averaged ultrasound intensities may not significantly benefit the adhesion of MB-cell complexes to the target vessel wall (p = NS), but could cause undesirable biologic effects such as heating to the MB-cell complexes and surrounding tissue. For the highest time-averaged ultrasound intensity of 6.60 W/cm², the temperature increase was 11.6 ± 1.3°C.
基于细胞的治疗方法对于修复受动脉粥样硬化影响或经血管成形术和支架置入术后的保护性内皮层具有吸引力。我们最近展示了一种新的技术，用于输送表面涂有阳离子脂质微泡（MB）的间充质干细胞（MSCs），并通过声辐射力（ARF）将其转移到动脉损伤部位。本研究的目的是确定有效的声基细胞疗法输送的超声参数。在血管流动体模中进行了体外实验，其中使用血管内超声导管产生的 ARF 将 MB 标记的 MSC 递送至体模壁。分析了 MB-细胞复合物的平移速度和粘附。实验数据表明，MSC 的径向速度和与血管体模的粘附随着时间平均超声强度增加到 1.65 W/cm²而增加，此后观察到没有进一步的显著粘附。在此设置下，导管附近的基线温度升高了 5.5±0.8°C。使用更高的时间平均超声强度可能不会显著有益于 MB-细胞复合物与靶血管壁的粘附（p=NS），但可能会导致不良的生物学效应，如对 MB-细胞复合物和周围组织的加热。对于最高时间平均超声强度为 6.60 W/cm²，温度升高了 11.6±1.3°C。
