The in vitro effects of a bimodal contrast agent on cellular functions and relaxometry

TY - JOUR

T1 - The in vitro effects of a bimodal contrast agent on cellular functions and relaxometry

AU - Brekke, Cecilie

AU - Morgan, Sarah C

AU - Lowe, Andrew S

AU - Meade, Thomas J

AU - Price, Jack

AU - Williams, Steve C R

AU - Modo, Michel

N1 - c 2006 John Wiley & Sons, Ltd.

PY - 2007/4

Y1 - 2007/4

N2 - 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.

AB - 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.

KW - Cell Movement

KW - Magnetic Resonance Imaging

KW - Animals

KW - Gadolinium

KW - Cell Differentiation

KW - Mice

KW - Contrast Media

KW - Cell Proliferation

KW - Reactive Oxygen Species

KW - Cell Survival

KW - Neurons

KW - Rhodamines

KW - Stem Cells

KW - Cell Line

KW - Dextrans

U2 - 10.1002/nbm.1077

DO - 10.1002/nbm.1077

M3 - Article

C2 - 16952123

VL - 20

SP - 77

EP - 89

JO - Nmr in Biomedicine

JF - Nmr in Biomedicine

IS - 2

ER -