Microbubble spectroscopy of microbubble-loaded stem cells for targeted cell therapy

Abstract

Stem cells can be conjugated with targeted microbubbles to form highly echogenic complexes, dubbed StemBells. The complexes can improve stem cell delivery for the local repair of damaged cardiac tissue after a myocardial infarction through propulsion by acoustic radiation forces. While the first in-vivo tests hold great promise, the system would greatly benefit from a mapping of the acoustic parameter space. Here, we develop the theoretical background based on a modified Rayleigh-Plesset type equation to describe the dynamics of the StemBells in response to ultrasound. The complex is shown to resonate as a whole entity and resonance curves are constructed from numerical simulations resembling single bubble responses at a size that relates to the effective complex radius ~10 μm. Ultra high-speed optical imaging of single StemBell complexes at different frequencies using the microbubble spectroscopy method allows for a full characterization with excellent agreement with the developed model. Moreover, from the experimental resonance curves, we obtain values for the effective viscoelastic shell parameters of the StemBell complexes. These results have enabled the demonstration of the feasibility of manipulating StemBells inside chicken embryo microvasculature in an accompanying paper.