In vivo MR imaging of intravascularly injected magnetically labeled mesenchymal stem cells in rat kidney and liver.
OBJECTIVE
To evaluate in vivo magnetic resonance (MR) imaging with a conventional 1.5-T system for depiction and tracking of intravascularly injected superparamagnetic iron oxide (SPIO)-labeled mesenchymal stem cells (MSCs).


METHODS
This study was conducted in accordance with French law governing animal research and met guidelines for animal care and use. Rat MSCs were labeled with SPIO and transfection agent. Relaxation rates at 1.5 T, cell viability, proliferation, differentiation capacity, and labeling stability were assessed in vitro as a function of SPIO concentration. MSCs were injected into renal arteries of healthy rats (labeled cells in four, unlabeled cells in two) and portal veins of rats treated with carbon tetrachloride to induce centrolobular liver necrosis (labeled cells and unlabeled cells in two each). Follow-up serial T2*-weighted gradient-echo MR imaging and R2* mapping were performed. MR imaging findings were compared histologically.


RESULTS
SPIO labeling caused a strong R2* effect that increased linearly with iron dose; R2* increase for cells labeled for 48 hours with 50 microg of iron per milliliter was 50 sec(-1) per million cells per milliliter. R2* was proportional to iron load of cells. SPIO labeling did not affect cell viability (P > .27). Labeled cells were able to differentiate into adipocytes and osteocytes. Proliferation was substantially limited for MSCs labeled with 100 microg Fe/mL or greater. Label half-life was longer than 11 days. In normal kidneys, labeled MSCs caused signal intensity loss in renal cortex. After labeled MSC injection, diseased liver had diffuse granular appearance. Cells were detected for up to 7 days in kidney and 12 days in liver. Signal intensity loss and fading over time were confirmed with serial R2* mapping. At histologic analysis, signal intensity loss correlated with iron-loaded cells, primarily in renal glomeruli and hepatic sinusoids; immunohistochemical analysis results confirmed these cells were MSCs.


CONCLUSIONS
MR imaging can aid in monitoring of intravascularly administered SPIO-labeled MSCs in vivo in kidney and liver.
Laboratoire d'Imagerie Moléculaire et Fonctionnelle, Equipes de Recherche Technologique, Centre National de la Recherche Scientifique, Université Victor Segalen Bordeaux-2, 146 rue Leo Saignat, Case 117, 33076 Bordeaux, France. clemens@imf.u-bordeaux2.fr
Clemens
C
Bos
Yahsou
Y
Delmas
Alexis
A
Desmoulière
Anne
A
Solanilla
Olivier
O
Hauger
Christophe
C
Grosset
Isabelle
I
Dubus
Zoran
Z
Ivanovic
Jean
J
Rosenbaum
Pierre
P
Charbord
Christian
C
Combe
Jeff W M
JW
Bulte
Chrit T W
CT
Moonen
Jean
J
Ripoche
Nicolas
N
Grenier
D017667:Adipocytes / Q000502:physiology; D000818:Animals; D002251:Carbon Tetrachloride / Q000009:adverse effects; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D003287:Contrast Media; D003911:Dextrans; D052203:Ferrosoferric Oxide; D007091:Image Processing, Computer-Assisted; D007202:Indicators and Reagents; D007501:Iron; D007668:Kidney / Q000166:cytology*; D007678:Kidney Glomerulus / Q000166:cytology; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009336:Necrosis; D010011:Osteocytes / Q000502:physiology; D010087:Oxides; D015642:Radiology, Interventional; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors
D003287:Contrast Media; D003911:Dextrans; D007202:Indicators and Reagents; D058185:Magnetite Nanoparticles; D010087:Oxides; D002251:Carbon Tetrachloride; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide