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Labeling human embryonic stem-cell-derived cardiomyocytes for tracking with MR imaging

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Abstract

Background

Human embryonic stem cells (hESC) can generate cardiomyocytes (CM), which offer promising treatments for cardiomyopathies in children. However, challenges for clinical translation result from loss of transplanted cell from target sites and high cell death. An imaging technique that noninvasively and repetitively monitors transplanted hESC-CM could guide improvements in transplantation techniques and advance therapies.

Objective

To develop a clinically applicable labeling technique for hESC-CM with FDA-approved superparamagnetic iron oxide nanoparticles (SPIO) by examining labeling before and after CM differentiation.

Materials and methods

Triplicates of hESC were labeled by simple incubation with 50 μg/ml of ferumoxides before or after differentiation into CM, then imaged on a 7T MR scanner using a T2-weighted multi-echo spin-echo sequence. Viability, iron uptake and T2-relaxation times were compared between groups using t-tests.

Results

hESC-CM labeled before differentiation demonstrated significant MR effects, iron uptake and preserved function. hESC-CM labeled after differentiation showed no significant iron uptake or change in MR signal (P < 0.05). Morphology, differentiation and viability were consistent between experimental groups.

Conclusion

hESC-CM should be labeled prior to CM differentiation to achieve a significant MR signal. This technique permits monitoring delivery and engraftment of hESC-CM for potential advancements of stem cell-based therapies in the reconstitution of damaged myocardium.

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Disclaimer

This study was supported by a research grant from the California Institute for Regenerative Medicine (CIRM), grant # RS1-00381-1.

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Authors and Affiliations

  1. Pediatric Radiology, Lucile Packard Children’s Hospital, Stanford School of Medicine, 725 Welch Rd, Rm 1665, Stanford, CA, 94305-5654, USA

    Rosalinda T. Castaneda & Heike Daldrup-Link

  2. Department of Radiology and Biomedical Imaging, UCSF Medical Center, University of California, San Francisco, CA, USA

    Sophie Boddington, Mike Wendland & Lydia Mandrussow

  3. Department of Radiology and Neuroradiology, University Hospital of Cologne, Cologne, Germany

    Tobias D. Henning

  4. Language Section, Voice, Speech and Language Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA

    Siyuan Liu

Authors
  1. Rosalinda T. Castaneda
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  2. Sophie Boddington
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  3. Tobias D. Henning
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  4. Mike Wendland
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  5. Lydia Mandrussow
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  6. Siyuan Liu
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Corresponding author

Correspondence to Heike Daldrup-Link.

Electronic supplementary material

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Successfully labeled, terminally differentiated, beating hESC-CM labeled with SPIO, ferumoxides, prior to CM differentiation. SPIO particles are seen in the cytoplasm of the labeled hESC-CM (MP4 13085 kb)

Terminally differentiated, beating hESC-CM that underwent attempted labeling following CM differentiation. No SPIO particles are visible in these hESC-CM (MP4 4698 kb)

Control, unlabeled, terminally differentiated, beating hESC-CM. No SPIO particles are present. These cells show no morphologic or functional difference compared to labeled cells in (1) (MP4 4072 kb)

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Castaneda, R.T., Boddington, S., Henning, T.D. et al. Labeling human embryonic stem-cell-derived cardiomyocytes for tracking with MR imaging. Pediatr Radiol 41, 1384–1392 (2011). https://doi.org/10.1007/s00247-011-2130-3

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  • DOI: https://doi.org/10.1007/s00247-011-2130-3

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