Acoustic radiation force for vascular stem cell therapy: An in vitro validation

Coronary stent placement and angioplasty may lead to vascular injury such as postprocedural stent thrombosis and restenosis. Mesenchymal stem cells (MSCs) have been reported to participate in effective restoration of functional endothelium following vascular injury. Our group has recently investigated a new technique for the delivery of MSCs to a site of arterial injury which involved surface-coating MSCs with cationic lipid microbubbles (MB) and directing them to target areas using acoustic radiation force (ARF). The objective of this study was to characterize ultrasound parameters for effective MSC delivery through in vitro experiments in which MB-labeled MSCs flowing through a phantom vessel were radially displaced towards the vessel wall using ARF applied with an intravascular ultrasound catheter driven at varying acoustic pressures and duty cycles. Experimental data indicated that MSC radial velocity was linearly related to the time-averaged ultrasound intensity up to 0.83 W/cm². Experimental data agreed with model predictions only up to this intensity level possibly due to MB destruction before the MB-MSC complexes reached the target area at high acoustic pressures. MSC adhesion to the phantom vessel wall increased with the time-averaged ultrasound intensity up to 1.65 W/cm², after which further adhesion did not occur. Using higher time-averaged ultrasound intensities may not substantially benefit the adhesion of complexes to the target vessel wall, but could cause undesirable biological effects such as heating to the MB-MSC complexes and surrounding tissue.