Abstract
We report on a new straightforward magnetic cell-labeling approach that combines three US Food and Drug Administration (FDA)-approved drugs--ferumoxytol, heparin and protamine--in serum-free medium to form self-assembling nanocomplexes that effectively label cells for in vivo magnetic resonance imaging (MRI). We observed that the ferumoxytol-heparin-protamine (HPF) nanocomplexes were stable in serum-free cell culture medium. HPF nanocomplexes show a threefold increase in T2 relaxivity compared to ferumoxytol. Electron microscopy showed internalized HPF in endosomes, which we confirmed by Prussian blue staining of labeled cells. There was no long-term effect or toxicity on cellular physiology or function of HPF-labeled hematopoietic stem cells, bone marrow stromal cells, neural stem cells or T cells when compared to controls. In vivo MRI detected 1,000 HPF-labeled cells implanted in rat brains. This HPF labeling method should facilitate the monitoring by MRI of infused or implanted cells in clinical trials.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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Apoptosis / drug effects
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Bone Marrow Cells / cytology
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Brain / cytology*
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Brain / diagnostic imaging
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Brain / ultrastructure
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Cell Differentiation / drug effects
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Cell Tracking / methods*
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Clinical Trials as Topic
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Culture Media, Serum-Free
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Endosomes / ultrastructure
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Ferrosoferric Oxide / administration & dosage
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Ferrosoferric Oxide / adverse effects
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Ferrosoferric Oxide / chemistry*
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Hematopoietic Stem Cells / cytology
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Heparin / administration & dosage
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Heparin / adverse effects
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Heparin / chemistry*
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Humans
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Magnetic Resonance Imaging
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Magnetite Nanoparticles / administration & dosage*
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Magnetite Nanoparticles / adverse effects*
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Magnetite Nanoparticles / chemistry*
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Magnetite Nanoparticles / ultrastructure
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Male
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Mesenchymal Stem Cells / cytology
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Microscopy, Electron
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Neurons / cytology
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Protamines / administration & dosage
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Protamines / adverse effects
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Protamines / chemistry*
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Radiography
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Rats
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Stem Cell Transplantation
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Stromal Cells / cytology
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T-Lymphocytes / cytology
Substances
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Culture Media, Serum-Free
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Magnetite Nanoparticles
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Protamines
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Heparin
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Ferrosoferric Oxide