Intravital microscopy of localized stem cell delivery using microbubbles and acoustic radiation force

ABSTRACT The use of stem cells for the repair of damaged cardiac tissue after a myocardial infarction holds great promise. However, a common finding in experimental studies is the low number of cells delivered at the area at risk. To improve the delivery, we are currently investigating a novel delivery platform in which stem cells are conjugated with targeted microbubbles, creating echogenic complexes dubbed StemBells. These StemBells vibrate in response to incoming ultrasound waves making them susceptible to acoustic radiation force. The acoustic force can then be employed to propel circulating StemBells from the centerline of the vessel to the wall, facilitating localized stem cell delivery. In this study, we investigate the feasibility of manipulating StemBells acoustically in vivo after injection using a chicken embryo model. Bare stem cells or unsaturated stem cells (30 bubbles/cell) can be propelled toward and arrested at the vessel wall. The mean translational velocities measured are 61 and 177 μm/s for P‐ = 200 and 450 kPa, respectively. This technique therefore offers potential for enhanced and well‐controlled stem cell delivery for improved cardiac repair after a myocardial infarction. Biotechnol. Bioeng. 2015;112: 220–227. © 2014 Wiley Periodicals, Inc. In this study the authors describe a novel local delivery platform for stem cells using targeted microbubble contrast agents and ultrasound therapy. By functionalizing microbubbles with specific antibodies, stem cells can be coated with microbubbles, creating echogenic complexes dubbed “StemBells.” In contrast to stem cells, StemBells are susceptible to acoustic radiation force. This force can then be employed to propel circulating StemBells from the centerline of the vessel toward the wall and arrest them in the region of interest.