title: Noninvasive monitoring of embryonic stem cells in vivo with MRI transgene reporter.
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 T(2)-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.
authors.affiliation: Neuroscience Program, Graduate Division of Biological and Biomedical Sciences, Emory University , Atlanta, GA 30322, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Eric C H
authors.initials: EC
authors.lastname: Cheng
authors.forename: Robert C
authors.initials: RC
authors.lastname: Long
authors.forename: Shang-Hsun
authors.initials: SH
authors.lastname: Yang
authors.forename: Liya
authors.initials: L
authors.lastname: Wang
authors.forename: Pei-Hsun
authors.initials: PH
authors.lastname: Cheng
authors.forename: Jinjing
authors.initials: J
authors.lastname: Yang
authors.forename: Dong
authors.initials: D
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Mao
authors.forename: Anthony W S
authors.initials: AW
authors.lastname: Chan
mesh_terms: D000818:Animals; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D017930:Genes, Reporter / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D009369:Neoplasms / Q000473:pathology; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D011180:Postmortem Changes; D019076:Transgenes / Q000235:genetics*
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins