title: Intravenous ferumoxytol allows noninvasive MR imaging monitoring of macrophage migration into stem cell transplants.
abstract: OBJECTIVE
  To develop a clinically applicable imaging technique for monitoring differential migration of macrophages into viable and apoptotic matrix-associated stem cell implants (MASIs) in arthritic knee joints.
  
  
  METHODS
  With institutional animal care and use committee approval, six athymic rats were injected with intravenous ferumoxytol (0.5 mmol iron per kilogram of body weight) to preload macrophages of the reticuloendothelial system with iron oxide nanoparticles. Forty-eight hours later, all animals received MASIs of viable adipose-derived stem cells (ADSCs) in an osteochondral defect of the right femur and mitomycin-pretreated apoptotic ADSCs in an osteochondral defect of the left femur. One additional control animal each received intravenous ferumoxytol and bilateral scaffold-only implants (without cells) or bilateral MASIs without prior ferumoxytol injection. All knees were imaged with a 7.0-T magnetic resonance (MR) imaging unit with T2-weighted fast spin-echo sequences immediately after, as well as 2 and 4 weeks after, matrix-associated stem cell implantation. Signal-to-noise ratios (SNRs) of viable and apoptotic MASIs were compared by using a linear mixed-effects model. MR imaging data were correlated with histopathologic findings.
  
  
  RESULTS
  All ADSC implants showed a slowly decreasing T2 signal over 4 weeks after matrix-associated stem cell implantation. SNRs decreased significantly over time for the apoptotic implants (SNRs on the day of matrix-associated stem cell implantation, 2 weeks after the procedure, and 4 weeks after the procedure were 16.9, 10.9, and 6.7, respectively; P = .0004) but not for the viable implants (SNRs on the day of matrix-associated stem cell implantation, 2 weeks after the procedure, and 4 weeks after the procedure were 17.7, 16.2, and 15.7, respectively; P = .2218). At 4 weeks after matrix-associated stem cell implantation, SNRs of apoptotic ADSCs were significantly lower than those of viable ADSCs (mean, 6.7 vs 15.7; P = .0013). This corresponded to differential migration of iron-loaded macrophages into MASIs.
  
  
  CONCLUSIONS
  Iron oxide loading of macrophages in the reticuloendothelial system by means of intravenous ferumoxytol injection can be utilized to monitor differential migration of bone marrow macrophages into viable and apoptotic MASIs in a rat model.
authors: Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, 725 Welch Rd, Room 1665, Stanford, CA 94305-5654, USA.
authors: Aman
authors: A
authors: Khurana
authors: Hossein
authors: H
authors: Nejadnik
authors: Rakhee
authors: R
authors: Gawande
authors: Guiting
authors: G
authors: Lin
authors: Sungmin
authors: S
authors: Lee
authors: Solomon
authors: S
authors: Messing
authors: Rosalinda
authors: R
authors: Castaneda
authors: Nikita
authors: N
authors: Derugin
authors: Laura
authors: L
authors: Pisani
authors: Tom F
authors: TF
authors: Lue
authors: Heike E
authors: HE
authors: Daldrup-Link
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D002478:Cells, Cultured; D004195:Disease Models, Animal; D052203:Ferrosoferric Oxide / Q000008:administration & dosage*; D017404:In Situ Hybridization, Fluorescence; D007267:Injections; D008262:Macrophage Activation; D008279:Magnetic Resonance Imaging / Q000379:methods*; D020370:Osteoarthritis, Knee / Q000276:immunology / Q000628:therapy*; D051381:Rats; D011923:Rats, Nude; D017207:Rats, Sprague-Dawley; D059629:Signal-To-Noise Ratio; D033581:Stem Cell Transplantation
chemical_list: D052203:Ferrosoferric Oxide