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cell acoustically active? The temporal course of acoustic activity needs to be
defined, with the preferable time course paralleling stem cell viability. The
mechanism of intracellular incorporation should be more fully understood
to optimize approaches to ensuring microbubble “survival” within the cell.
For example, if endocytosis is involved, a strategy for inducing lysosomal
“escape” might be helpful for preventing microbubble destruction once
internalized by the cell. Acoustic characterization of the microbubble-cell
complexes using a combination of spectral analysis, ultrasound imaging,
and ultra-high-speed microscopic imaging [29,30] under various ultrasound
transmission parameters will be important for optimizing algorithms for
detecting signals specific to labeled stem cells. Such acoustic parameters will
ultimately need to be built into clinical scanning systems.
16.8 Conclusion
The determination of stem cell fate after exogenous delivery is important to the
clinical implementation of cell-based therapies. Microbubble probes and ultra-
sound imaging may offer unique advantages for real-time, serial stem cell track-
ing in patients. Important proofs of concept have already been demonstrated.
Further advances in microbubble chemistry and imaging technology along the
lines described should facilitate clinical realization of this imaging approach
and assist in the development of cell therapies for human populations.
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5. Hundley, W.G., Kizilbash, A.M., Afridi, I., et al. 1998. Administration of an intra-
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