title: Acoustic radiation force for vascular cell therapy: in vitro validation.
abstract: 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.
authors.affiliation: Center for Ultrasound Molecular Imaging and Therapeutics, Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kaya
authors.forename: Catalin
authors.initials: C
authors.lastname: Toma
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wang
authors.forename: Michelle
authors.initials: M
authors.lastname: Grata
authors.forename: Huili
authors.initials: H
authors.lastname: Fu
authors.forename: Flordeliza S
authors.initials: FS
authors.lastname: Villanueva
authors.forename: Xucai
authors.initials: X
authors.lastname: Chen
mesh_terms: D001808:Blood Vessels / Q000166:cytology* / Q000254:growth & development*; D002469:Cell Separation / Q000379:methods*; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D019220:High-Energy Shock Waves; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology* / Q000528:radiation effects*; D011829:Radiation Dosage