In vitro evaluation of magnetic resonance imaging contrast agents for labeling human liver cells: implications for clinical translation.
OBJECTIVE
Magnetic resonance imaging (MRI) is a promising approach for non-invasive monitoring after liver cell transplantation. We compared in vitro labeling of human liver cells with nano-sized (SPIO) and micron-sized iron oxide particles (MPIO).


METHODS
The cellular iron load was quantified and phantom studies were performed using 3.0-T MRI. Transferrin receptor and ferritin gene expression, reactive oxygen species (ROS) formation, transaminase leakage, and urea synthesis were investigated over 6 days.


RESULTS
Incubation with MPIO produced stronger signal extinctions in MRI at similar iron loads within shorter labeling time. MPIO had no negative effects on the cellular iron homeostasis or cell performance, whereas SPIO caused temporary ROS formation and non-physiologic activation of the iron metabolic pathway.


CONCLUSIONS
Our findings suggest that MPIO are suited for clinical translation of strategies for cellular imaging with MRI. Attention should be paid to iron release and oxidative stress caused by biodegradable contrast agents.
Raschzok
Nathanael
N
General, Visceral, and Transplantation Surgery, Experimental Surgery and Regenerative Medicine, Charité-Campus Virchow, Universitätsmedizin Berlin, Berlin, Germany. nathanael.raschzok@charite.de
Muecke
David A
DA
Adonopoulou
Michaela K
MK
Billecke
Nils
N
Werner
Wiebke
W
Kammer
Nora N
NN
Zielinski
Anja
A
Behringer
Peter A
PA
Ringel
Frauke
F
Huang
Mao D
MD
Neuhaus
Peter
P
Teichgräber
Ulf
U
Sauer
Igor M
IM
D003287:Contrast Media / Q000378:metabolism*; D005293:Ferritins / Q000235:genetics / Q000378:metabolism; D052203:Ferrosoferric Oxide / Q000378:metabolism; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000166:cytology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D013194:Staining and Labeling; D057170:Translational Research, Biomedical
D003287:Contrast Media; D017382:Reactive Oxygen Species; D011990:Receptors, Transferrin; D005293:Ferritins; D007501:Iron; D052203:Ferrosoferric Oxide