title: Iron administration before stem cell harvest enables MR imaging tracking after transplantation.
abstract: OBJECTIVE
  To determine whether intravenous ferumoxytol can be used to effectively label mesenchymal stem cells (MSCs) in vivo and can be used for tracking of stem cell transplants.
  
  
  METHODS
  This study was approved by the institutional animal care and use committee. Sprague-Dawley rats (6-8 weeks old) were injected with ferumoxytol 48 hours prior to extraction of MSCs from bone marrow. Ferumoxytol uptake by these MSCs was evaluated with fluorescence, confocal, and electron microscopy and compared with results of traditional ex vivo-labeling procedures. The in vivo-labeled cells were subsequently transplanted in osteochondral defects of 14 knees of seven athymic rats and were evaluated with magnetic resonance (MR) imaging up to 4 weeks after transplantation. T2 relaxation times of in vivo-labeled MSC transplants and unlabeled control transplants were compared by using t tests. MR data were correlated with histopathologic results.
  
  
  RESULTS
  In vivo-labeled MSCs demonstrated significantly higher ferumoxytol uptake compared with ex vivo-labeled cells. With electron microscopy, iron oxide nanoparticles were localized in secondary lysosomes. In vivo-labeled cells demonstrated significant T2 shortening effects in vitro and in vivo when they were compared with unlabeled control cells (T2 in vivo, 15.4 vs 24.4 msec; P < .05) and could be tracked in osteochondral defects for 4 weeks. Histologic examination confirmed the presence of iron in labeled transplants and defect remodeling.
  
  
  CONCLUSIONS
  Intravenous ferumoxytol can be used to effectively label MSCs in vivo and can be used for tracking of stem cell transplants with MR imaging. This method eliminates risks of contamination and biologic alteration of MSCs associated with ex vivo-labeling procedures.
authors.affiliation: Department of Radiology and Molecular Imaging Program at Stanford, Stanford University School of Medicine, 725 Welch Rd, Room 1665, Stanford, CA 94305-5654; Department of Communication and Statistics and Department of Materials Science and Engineering, Stanford University, Stanford, Calif; Department of Neurology, Comprehensive Cancer Center, Cardiovascular Research Institute and Department of Anatomy, University of California San Francisco, San Francisco, Calif.
authors.forename: Aman
authors.initials: A
authors.lastname: Khurana
authors.forename: Fanny
authors.initials: F
authors.lastname: Chapelin
authors.forename: Graham
authors.initials: G
authors.lastname: Beck
authors.forename: Olga D
authors.initials: OD
authors.lastname: Lenkov
authors.forename: Jessica
authors.initials: J
authors.lastname: Donig
authors.forename: Hossein
authors.initials: H
authors.lastname: Nejadnik
authors.forename: Solomon
authors.initials: S
authors.lastname: Messing
authors.forename: Nikita
authors.initials: N
authors.lastname: Derugin
authors.forename: Ray Chun-Fai
authors.initials: RC
authors.lastname: Chan
authors.forename: Amitabh
authors.initials: A
authors.lastname: Gaur
authors.forename: Barbara
authors.initials: B
authors.lastname: Sennino
authors.forename: Donald M
authors.initials: DM
authors.lastname: McDonald
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kempen
authors.forename: Grigory A
authors.initials: GA
authors.lastname: Tikhomirov
authors.forename: Jianghong
authors.initials: J
authors.lastname: Rao
authors.forename: Heike E
authors.initials: HE
authors.lastname: Daldrup-Link
mesh_terms: D000818:Animals; D002469:Cell Separation; D058948:Cell Tracking / Q000379:methods*; D002478:Cells, Cultured; D003287:Contrast Media / Q000008:administration & dosage; D052203:Ferrosoferric Oxide / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling / Q000379:methods; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology*
chemical_list: D003287:Contrast Media; D052203:Ferrosoferric Oxide