title: In vivo magnetic resonance imaging of iron oxide-labeled, intravenous-injected mesenchymal stem cells in kidneys of rabbits with acute ischemic kidney injury: detection and monitoring at 1.5 T.
abstract: BACKGROUND
  Acute kidney injury (AKI) is one of the most important causes of mortality and morbidity worldwide. Mesenchymal stem cells (MSCs) can be used for stem cell-based therapy containing AKI. Magnetic resonance imaging (MRI) is an ideal mean for stem cells tracking by labeling with superparamagnetic iron oxide (SPIO). Therefore, using the iron oxide-labeled mesenchymal stem cells (MSC) to treat the AKI and evaluating migration, distribution, and homing of cells by MRI is an ideal method for cell therapy and cell tracking in vivo.
  
  
  METHODS
  In vitro, the MSCs were labeled with 25 μg/mL for 24 h, and test the labeled efficiency and cells viability. In vitro experiments, magnetic resonance imaging (MRI) measurement of non-labeled and SPIO-labeled MSCs (SPIO-MSCs) was performed in correlation to detectable cells concentrations and detectable time windows. In vivo experiments, MRI evaluation was performed before and after ischemic/reperfusion AKI (N = 14) and intravenous injection of 5 × 10(5) SPIO-MSCs (N = 10), PBS (N = 6) up to 8 days using a clinical 1.5 T scanner. Signal intensity of kidneys were measured and tested for statistical significance (unpaired Student's t-test, p < 0.05) in comparison histology (hematoxylin and eosin [H&E], Prussian blue).
  
  
  RESULTS
  In vitro, MSCs can be labeled with the SPIO without affecting the viability and labeling efficiency. SPIO-MSCs showed a reduction of signal intensity at T2WI and T2*WI, 5 × 10(4) cells/mL, SPIO-MSCs were the minimum imaging cells concentration using a 1.5 T MR in vitro. In vivo, SPIO-MSCs administration resulted in a T2*WI signal intensity decrease in renal medulla caused by SPIO-MSCs accumulation in contrast to control groups (p < 0.05) up to day 3 after transplantation, but T2*WI low signal intensity region of the renal medulla revealed an decrease at day 5, and no significant differences between SPIO-MSCs and control animals at day 8.
  
  
  CONCLUSIONS
  Our data demonstrate that in vitro and in vivo, cell-tracking and monitoring of kidney distribution of intravenous injected SPIO-MSCs after AKI is feasible in MRI at 1.5 T.
authors.affiliation: a Department of Radiology , First Clinical Medical School of Shanxi Medical University , Taiyuan , Shanxi , China .
authors.forename: Ruiping
authors.initials: R
authors.lastname: Zhang
authors.affiliation: b State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences , Beijing , China .
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: c Department of Radiology , First Hospital, Shanxi Tumor Hospital , Taiyuan , Shanxi , China , and.
authors.forename: Lei
authors.initials: L
authors.lastname: Xin
authors.affiliation: d Department of Molecular Biology , Shanxi Medical University , Taiyuan , Shanxi , China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology* / Q000628:therapy*; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D003287:Contrast Media / Q000008:administration & dosage; D003911:Dextrans / Q000008:administration & dosage*; D004195:Disease Models, Animal; D007275:Injections, Intravenous; D007668:Kidney / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000008:administration & dosage*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D011817:Rabbits; D013194:Staining and Labeling
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C065507:ferumoxides
keywords: Acute kidney injury; iron oxide particles; magnetic resonance imaging; mesenchymal stem cells