In vivo tracking of human neural progenitor cells in the rat brain using magnetic resonance imaging is not enhanced by ferritin expression

Ksenija Bernau, Christina M. Lewis, Anna M. Petelinsek, Matthew S. Reagan, David J. Niles, Virginia B. Mattis, M. Elizabeth Meyerand, Masatoshi Suzuki, Clive N. Svendsen

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Rapid growth in the field of stem cell research has generated a lot of interest in their therapeutic use, especially in the treatment of neurodegenerative diseases. Specifically, human neural progenitor cells (hNPCs), unique in their capability to differentiate into cells of the neural lineage, have been widely investigated due to their ability to survive, thrive, and migrate toward injured tissues. Still, one of the major roadblocks for clinical applicability arises from the inability to monitor these cells following transplantation. Molecular imaging techniques, such as magnetic resonance imaging (MRI), have been explored to assess hNPC transplant location, migration, and survival. Here we investigated whether inducing hNPCs to overexpress ferritin (hNPCsFer), an iron storage protein, is sufficient to track these cells long term in the rat striatum using MRI. We found that increased hypointensity on MRI images could establish hNPCFer location. Unexpectedly, however, wild-type hNPC transplants were detected in a similar manner, which is likely due to increased iron accumulation following transplantation-induced damage. Hence, we labeled hNPCs with superparamagnetic iron oxide (SPIO) nanoparticles to further increase iron content in an attempt to enhance cell contrast in MRI. SPIO-labeling of hNPCs (hNPCs-SPIO) achieved increased hypointensity, with significantly greater area of decreased T2* compared to hNPCFer (p < 0.0001) and all other controls used. However, none of the techniques could be used to determine graft rejection in vivo, which is imperative for understanding cell behavior following transplantation. We conclude that in order for cell survival to be monitored in preclinical and clinical settings, another molecular imaging technique must be employed, including perhaps multimodal imaging, which would utilize MRI along with another imaging modality.

Original languageEnglish (US)
Pages (from-to)575-592
Number of pages18
JournalCell transplantation
Volume25
Issue number3
DOIs
StatePublished - 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 Cognizant, LLC.

Keywords

  • Cell tracking
  • Ferritin
  • Magnetic resonance imaging (MRI)
  • Neural progenitor cells
  • Superparamagnetic iron oxide (SPIO)

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