StemBells: Localized stem cell delivery using targeted microbubbles and acoustic radiation force

Abstract

The use of stem cells for regenerative tissue repair is hampered by the low number of cells delivered to the site of injury. To increase the delivery, we developed a new technique in which stem cells are coated with functionalized microbubbles, creating echogenic complexes dubbed StemBells. StemBells are highly susceptible to acoustic radiation force; this acoustic force can then be used after injection to deliver the StemBells locally at the treatment site. The dynamics of StemBells during ultrasound insonification was characterized using high-speed optical imaging and is described in an accompanying paper. Here, we investigate the feasibility of manipulating StemBells acoustically after injection employing a chicken embryo model, allowing for the real-time optical observation of the effects of acoustic radiation force in vivo. StemBells were infused by placing a custom-made catheter into one of the vitelline veins. Acoustic radiation force (1 MHz, P = 200–450 kPa, 10% duty cycle) was observed to propel StemBells from the centerline of the microvessels (200–500 μm) to the wall distal from the transducer. Peak translational velocities increased with pressure and varied between 50 μm/s to 300 μm/s. The acoustic radiation force had no effect on the trajectory of bare stem cells.