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Pediatric Radiology

, Volume 41, Issue 11, pp 1384–1392 | Cite as

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

  • Rosalinda T. Castaneda
  • Sophie Boddington
  • Tobias D. Henning
  • Mike Wendland
  • Lydia Mandrussow
  • Siyuan Liu
  • Heike Daldrup-LinkEmail author
Original Article

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.

Keywords

Human embryonic stem cells Cardiomyocytes Iron oxides SPIO MR imaging Cell labeling Children 

Notes

Disclaimer

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

Supplementary material

Online Resource 1

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)

Online Resource 2

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

Online Resource 3

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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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Rosalinda T. Castaneda
    • 1
  • Sophie Boddington
    • 2
  • Tobias D. Henning
    • 3
  • Mike Wendland
    • 2
  • Lydia Mandrussow
    • 2
  • Siyuan Liu
    • 4
  • Heike Daldrup-Link
    • 1
    Email author
  1. 1.Pediatric RadiologyLucile Packard Children’s Hospital, Stanford School of MedicineStanfordUSA
  2. 2.Department of Radiology and Biomedical Imaging, UCSF Medical CenterUniversity of CaliforniaSan FranciscoUSA
  3. 3.Department of Radiology and NeuroradiologyUniversity Hospital of CologneCologneGermany
  4. 4.Language Section, Voice, Speech and Language Branch, National Institute on Deafness and Other Communication DisordersNational Institutes of HealthBethesdaUSA

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