title: The in vitro effects of a bimodal contrast agent on cellular functions and relaxometry.
abstract: The in vivo monitoring of cell survival and migration will be essential to the translation of cell-based therapies from the laboratory to clinical studies. The pre-labeling of cells with magnetic resonance imaging (MRI) contrast agents renders them visible in vivo for serial cellular imaging. However, little is known about the impact of the presence of these metal particles inside transplanted cells. The use of the bimodal contrast agent GRID made it possible to demonstrate by means of fluorescent microscopy and inductively coupled plasma mass spectrometry (ICP-MS) that, after 16 h of incubation (without the use of a transfection agent), neural stem cells (NSCs) were saturated and no longer incorporated particles. With this maximal uptake, no significant effect on cell viability was observed. However, a significant decrease in proliferation was evident in cells that underwent 24 h of labeling. A significant increase in reactive oxygen species was observed for all GRID labeling, with a very significant increase with 24 h of labeling. GRID labeling did not affect cell motility in comparison with PKH26-labeled NSCs in a glioma-based migration assay and also allowed differentiation into all major cell types of the brain. GRID-labeled cells induced a signal change of 47% on T(2) measurements and allows a detection of cell clusters of approximately 220 cells/microl. Further in vivo testing will be required to ensure that cell labeling with gadolinium-based MRI contrast agents does not impair their ability to repair.
authors.affiliation: NeuroImaging Research Group - Department of Neurology, Institute of Psychiatry, King's College London, UK.
authors.forename: Cecilie
authors.initials: C
authors.lastname: Brekke
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Morgan
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Lowe
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Meade
authors.forename: Jack
authors.initials: J
authors.lastname: Price
authors.forename: Steve C R
authors.initials: SC
authors.lastname: Williams
authors.forename: Michel
authors.initials: M
authors.lastname: Modo
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000494:pharmacology*; D003911:Dextrans / Q000494:pharmacology*; D005682:Gadolinium / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D009474:Neurons / Q000166:cytology; D017382:Reactive Oxygen Species; D012235:Rhodamines / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology
chemical_list: D003287:Contrast Media; D003911:Dextrans; D017382:Reactive Oxygen Species; D012235:Rhodamines; C051311:rhodamine dextran; D005682:Gadolinium