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Quantification of MRI signal of transgenic grafts overexpressing ferritin in murine myocardial infarcts

Authors

  • Anna V. Naumova,

    Corresponding author
    1. Department of Radiology, University of Washington, Seattle, WA, USA
    2. Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA
    • Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA
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  • Vasily L. Yarnykh,

    1. Department of Radiology, University of Washington, Seattle, WA, USA
    2. Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA
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  • Niranjan Balu,

    1. Department of Radiology, University of Washington, Seattle, WA, USA
    2. Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA
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  • Hans Reinecke,

    1. Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA
    2. Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA
    3. Department of Pathology, University of Washington, Seattle, WA, USA
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  • Charles E. Murry,

    1. Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA
    2. Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA
    3. Department of Pathology, University of Washington, Seattle, WA, USA
    4. Department of Bioengineering, University of Washington, Seattle, WA, USA
    5. Department of Medicine/Cardiology, University of Washington, Seattle, WA, USA
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  • Chun Yuan

    1. Department of Radiology, University of Washington, Seattle, WA, USA
    2. Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA
    3. Department of Bioengineering, University of Washington, Seattle, WA, USA
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A. V. Naumova, University of Washington, 815 Mercer Street, Brotman Building, Room 124, Seattle, WA 98109, USA.

E-mail: nav@uw.edu

Abstract

The noninvasive detection of transplanted cells in damaged organs and the longitudinal follow-up of cell fate and graft size are important for the evaluation of cell therapy. We have shown previously that the overexpression of the natural iron storage protein, ferritin, permits the detection of engrafted cells in mouse heart by MRI, but further imaging optimization is required. Here, we report a systematic evaluation of ferritin-based stem cell imaging in infarcted mouse hearts in vivo using three cardiac-gated pulse sequences in a 3-T scanner: black-blood proton-density-weighted turbo spin echo (PD TSE BB), bright-blood T2*-weighted gradient echo (GRE) and black-blood T2*-weighted GRE with improved motion-sensitized-driven equilibrium (iMSDE) preparation. Transgenic C2C12 myoblast grafts overexpressing ferritin did not change MRI contrast in the PD TSE BB images, but showed a 20% reduction in signal intensity ratio in black-blood T2*-weighted iMSDE (p < 0.05) and a 30% reduction in bright-blood T2*-weighted GRE (p < 0.0001). Graft size measurements by T2* iMSDE and T2* GRE were highly correlated with histological assessments (r = 0.79 and r = 0.89, respectively). Unlabeled wild-type C2C12 cells transplanted to mouse heart did not change the MRI signal intensity, although endogenous hemosiderin was seen in some infarcts. These data support the use of ferritin to track the survival, growth and migration of stem cells transplanted into the injured heart. Copyright © 2012 John Wiley & Sons, Ltd.

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