Magnetic resonance imaging of iron oxide-labeled human embryonic stem cell-derived cardiac progenitors

Rhys J.P. Skelton, Suhail Khoja, Shone Almeida, Stanislas Rapacchi, Fei Han, James Engel, Peng Zhao, Peng Hu, Edouard G. Stanley, Andrew G. Elefanty, Murray Kwon, David A. Elliott, Reza Ardehali

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

Abstract

Given the limited regenerative capacity of the heart, cellular therapy with stem cell-derived cardiac cells could be a potential treatment for patients with heart disease. However, reliable imaging techniques to longitudinally assess engraftment of the transplanted cells are scant. To address this issue, we used ferumoxytol as a labeling agent of human embryonic stem cell-derived cardiac progenitor cells (hESC-CPCs) to facilitate tracking by magnetic resonance imaging (MRI) in a large animal model. Differentiating hESCs were exposed to ferumoxytol at different time points and varying concentrations. We determined that treatment with ferumoxytol at 300 μg/ml on day 0 of cardiac differentiation offered adequate cell viability and signal intensity for MRI detection without compromising further differentiation into definitive cardiac lineages. Labeled hESC-CPCs were transplanted by open surgical methods into the left ventricular free wall of uninjured pig hearts and imaged both ex vivo and in vivo. Comprehensive T2*-weighted images were obtained immediately after transplantation and 40 days later before termination. The localization and dispersion of labeled cells could be effectively imaged and tracked at days 0 and 40 by MRI. Thus, under the described conditions, ferumoxytol can be used as a long-term, differentiation-neutral cell-labeling agent to track transplanted hESC-CPCs in vivo using MRI.

Original languageEnglish
Pages (from-to)67-74
Number of pages8
JournalStem Cells Translational Medicine
Volume5
Issue number1
DOIs
Publication statusPublished - 2016
Externally publishedYes

Keywords

  • Cardiac stem cell biology
  • Cardiovascular progenitors
  • Cell labeling
  • Magnetic resonance imaging
  • Stem cell therapy

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