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Imaging approaches for the study of cell-based cardiac therapies

Abstract

Despite promising preclinical data, the treatment of cardiovascular diseases using embryonic, bone-marrow-derived, and skeletal myoblast stem cells has not yet come to fruition within mainstream clinical practice. Major obstacles in cardiac stem cell investigations include the ability to monitor cell engraftment and survival following implantation within the myocardium. Several cellular imaging modalities, including reporter gene and MRI-based tracking approaches, have emerged that provide the means to identify, localize, and monitor stem cells longitudinally in vivo following implantation. This Review will examine the various cardiac cellular tracking modalities, including the combinatorial use of several probes in multimodality imaging, with a focus on data from the past 5 years.

Key Points

  • Two groups of contrast agents, superparamagnetic iron oxide nanoparticles (SPIOs) and to a lesser degree the gadolinium chelates, enable detection of cardiac stem cell populations by MRI following implantation

  • Currently, clinical application of in vivo tracking using SPIOs or gadolinium chelates in cardiovascular disease has several limitations

  • The ability to correlate cell viability with signals from radionuclide probes and reporter genes is a major advantage, although in vivo use of reporter genes is currently limited to animal models

  • Multimodality approaches combining both iron-based and radionuclide probes offer increased sensitivity and specificity for stem cell localization and tracking

  • Protocols using MRI and reporter genes to monitor stem cell transplantation are being developed and translation to the clinic will require nonimmunogenic probes that are stably expressed after implantation

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Figure 1: ES-CPCs labeled with SPIOs.
Figure 2: Evaluation of noninfarcted mice.
Figure 3: PET-CT imaging of intramyocardial reporter gene expression.

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Acknowledgements

This work was supported in part by the intramural research program of the National Heart Lung and Blood Institute and the Clinical Center at the NIH.

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Correspondence to Joseph A. Frank.

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Lau, J., Anderson, S., Adler, E. et al. Imaging approaches for the study of cell-based cardiac therapies. Nat Rev Cardiol 7, 97–105 (2010). https://doi.org/10.1038/nrcardio.2009.227

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