In vivo magnetic resonance imaging of iron oxide-labeled, arterially-injected mesenchymal stem cells in kidneys of rats with acute ischemic kidney injury: detection and monitoring at 3T.
OBJECTIVE
To evaluate MRI for a qualitative and quantitative in vivo tracking of intraaortal injected iron oxide-labeled mesenchymal stem cells (MSC) into rats with acute kidney injury (AKI).


METHODS
In vitro MRI and R2* measurement of nonlabeled and superparamagnetic iron oxide (SPIO)-labeled MSC (MSC(SPIO)) was performed in correlation to cellular iron content and cytological examination (Prussian blue, electron microscopy). In vivo MRI and R2* evaluation were performed before and after ischemic/reperfusion AKI (N = 14) and intraaortal injection of 1.5 x 10(6) MSC(SPIO) (N = 7), fetal calf serum (FCS) (medium, N = 6), and SPIO alone (N = 1) up to 14 days using a clinical 3T scanner. Signal to noise ratios (SNR), R2* of kidneys, liver, spleen, and bone marrow, renal function (creatinine [CREA], blood urea nitrogen [BUN]), and kidney volume were measured and tested for statistical significance (Student's t-test, P < 0.05) in comparison histology (hematoxylin and eosin [H&E], Prussian blue, periodic acid-Schiff [PAS], CD68).


RESULTS
In vitro, MSC(SPIO) showed a reduction of SNR and T2* with R2* approximately number of MSC(SPIO) (R2 = 0.98). In vivo MSC(SPIO) administration resulted in a SNR decrease (35 +/- 15%) and R2* increase (101 +/- 18.3%) in renal cortex caused by MSC(SPIO) accumulation in contrast to control animals (P < 0.01). Liver, spleen, and bone marrow (MSC(SPIO)) showed a delayed SNR decline/R2* increase (P < 0.05) resulting from MSC(SPIO) migration. The increase of kidney volume and the decrease in renal function (P < 0.05) was reduced in MSC-treated animals.


CONCLUSIONS
Qualitative and quantitative in vivo cell-tracking and monitoring of organ distribution of intraaortal injected MSC(SPIO) in AKI is feasible in MRI at 3T.
Ittrich
Harald
H
Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, DE-20246 Hamburg, Germany. ittrich@uke.uni-hamburg.de
Lange
Claudia
C
Tögel
Florian
F
Zander
Axel R
AR
Dahnke
Hannes
H
Westenfelder
Christof
C
Adam
Gerhard
G
Nolte-Ernsting
Claus
C
D000818:Animals; D003287:Contrast Media; D003911:Dextrans; D005240:Feasibility Studies; D052203:Ferrosoferric Oxide; D007091:Image Processing, Computer-Assisted; D007269:Injections, Intra-Arterial; D007501:Iron; D007511:Ischemia / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy*; D007668:Kidney / Q000166:cytology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D045164:Mesenchymal Stem Cell Transplantation; D010087:Oxides; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide