Noninvasive monitoring of embryonic stem cells in vivo with MRI transgene reporter

Jun Liu, Eric C.H. Cheng, Robert C. Long, Shang Hsun Yang, Liya Wang, Pei Hsun Cheng, Jinjing Yang, Dong Wu, Hui Mao, Anthony W.S. Chan

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)

Abstract

Reporter gene-based magnetic resonance imaging (MRI) offers unique insights into behavior of cells after transplantation, which could significantly benefit stem cell research and translation. Several candidate MRI reporter genes, including one that encodes for iron storage protein ferritin, have been reported, and their potential applications in embryonic stem (ES) cell research have yet to be explored. We have established transgenic mouse ES (mES) cell lines carrying human ferritin heavy chain (FTH) as a reporter gene and succeeded in monitoring the cell grafts in vivo using T2-weighted MRI sequences. FTH generated MRI contrast through compensatory upregulation of transferrin receptor (Tfrc) that led to increased cellular iron stored in ferritin-bound form. At a level sufficient for MRI contrast, expression of FTH posed no toxicity to mES cells and did not interfere with stem cell pluripotency as observed in neural differentiation and teratoma formation. The compatibility and functionality of ferritin as a reporter in mES cells opens up the possibility of using MRI for longitudinal noninvasive monitoring of ES cell-derived cell grafts at both molecular and cellular levels.

Original languageEnglish
Pages (from-to)739-747
Number of pages9
JournalTissue Engineering - Part C: Methods
Volume15
Issue number4
DOIs
Publication statusPublished - 2009 Dec 1

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering

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