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

J Magn Reson Imaging. 2007 Jun;25(6):1179-91. doi: 10.1002/jmri.20925.

Abstract

Purpose: 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).

Materials and 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.

Conclusion: 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.

MeSH terms

  • Animals
  • Contrast Media
  • Dextrans
  • Feasibility Studies
  • Ferrosoferric Oxide
  • Image Processing, Computer-Assisted
  • Injections, Intra-Arterial
  • Iron
  • Ischemia / diagnosis*
  • Ischemia / physiopathology
  • Ischemia / therapy*
  • Kidney / cytology*
  • Magnetic Resonance Imaging / methods*
  • Magnetite Nanoparticles
  • Mesenchymal Stem Cell Transplantation*
  • Oxides
  • Rats
  • Rats, Sprague-Dawley
  • Staining and Labeling

Substances

  • Contrast Media
  • Dextrans
  • Magnetite Nanoparticles
  • Oxides
  • Iron
  • ferumoxides
  • Ferrosoferric Oxide