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Self-assembling nanocomplexes by combining ferumoxytol, heparin and protamine for cell tracking by magnetic resonance imaging

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 imag... Full description

Journal Title: Nature medicine 2012, Vol.18 (3), p.463-467
Main Author: Thu, Mya S
Other Authors: Bryant, L Henry , Coppola, Tiziana , Jordan, E Kay , Budde, Matthew D , Lewis, Bobbi K , Chaudhry, Aneeka , Ren, Jiaqiang , Varma, Nadimpalli Ravi S , Arbab, Ali S , Frank, Joseph A
Format: Electronic Article Electronic Article
Language: English
Subjects:
NMR
Publisher: United States: Nature Publishing Group
ID: ISSN: 1078-8956
Link: https://www.ncbi.nlm.nih.gov/pubmed/22366951
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title: Self-assembling nanocomplexes by combining ferumoxytol, heparin and protamine for cell tracking by magnetic resonance imaging
format: Article
creator:
  • Thu, Mya S
  • Bryant, L Henry
  • Coppola, Tiziana
  • Jordan, E Kay
  • Budde, Matthew D
  • Lewis, Bobbi K
  • Chaudhry, Aneeka
  • Ren, Jiaqiang
  • Varma, Nadimpalli Ravi S
  • Arbab, Ali S
  • Frank, Joseph A
subjects:
  • Animals
  • Apoptosis - drug effects
  • Biomedical research
  • Bone Marrow Cells - cytology
  • Brain - cytology
  • Brain - diagnostic imaging
  • Brain - ultrastructure
  • Cell Differentiation - drug effects
  • Cell Tracking - methods
  • Cellular biology
  • Clinical Trials as Topic
  • Complications and side effects
  • Culture Media, Serum-Free
  • Dosage and administration
  • Endosomes - ultrastructure
  • Ferrosoferric Oxide - administration & dosage
  • Ferrosoferric Oxide - adverse effects
  • Ferrosoferric Oxide - chemistry
  • Hematopoietic Stem Cells - cytology
  • Heparin
  • Heparin - administration & dosage
  • Heparin - adverse effects
  • Heparin - chemistry
  • Humans
  • Magnetic Resonance Imaging
  • Magnetite Nanoparticles - administration & dosage
  • Magnetite Nanoparticles - adverse effects
  • Magnetite Nanoparticles - chemistry
  • Magnetite Nanoparticles - ultrastructure
  • Male
  • Mesenchymal Stromal Cells - cytology
  • Microscopy, Electron
  • Nanotechnology
  • Neurons - cytology
  • NMR
  • Nuclear magnetic resonance
  • Pharmacology
  • Protamines - administration & dosage
  • Protamines - adverse effects
  • Protamines - chemistry
  • Radiography
  • Rats
  • Stem Cell Transplantation
  • Stromal Cells - cytology
  • T-Lymphocytes - cytology
  • Usage
ispartof: Nature medicine, 2012, Vol.18 (3), p.463-467
description: 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.
language: eng
source:
identifier: ISSN: 1078-8956
fulltext: no_fulltext
issn:
  • 1078-8956
  • 1546-170X
url: Link


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titleSelf-assembling nanocomplexes by combining ferumoxytol, heparin and protamine for cell tracking by magnetic resonance imaging
creatorThu, Mya S ; Bryant, L Henry ; Coppola, Tiziana ; Jordan, E Kay ; Budde, Matthew D ; Lewis, Bobbi K ; Chaudhry, Aneeka ; Ren, Jiaqiang ; Varma, Nadimpalli Ravi S ; Arbab, Ali S ; Frank, Joseph A
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descriptionWe 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.
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subjectAnimals ; Apoptosis - drug effects ; Biomedical research ; Bone Marrow Cells - cytology ; Brain - cytology ; Brain - diagnostic imaging ; Brain - ultrastructure ; Cell Differentiation - drug effects ; Cell Tracking - methods ; Cellular biology ; Clinical Trials as Topic ; Complications and side effects ; Culture Media, Serum-Free ; Dosage and administration ; Endosomes - ultrastructure ; Ferrosoferric Oxide - administration & dosage ; Ferrosoferric Oxide - adverse effects ; Ferrosoferric Oxide - chemistry ; Hematopoietic Stem Cells - cytology ; Heparin ; Heparin - administration & dosage ; Heparin - adverse effects ; Heparin - chemistry ; Humans ; Magnetic Resonance Imaging ; Magnetite Nanoparticles - administration & dosage ; Magnetite Nanoparticles - adverse effects ; Magnetite Nanoparticles - chemistry ; Magnetite Nanoparticles - ultrastructure ; Male ; Mesenchymal Stromal Cells - cytology ; Microscopy, Electron ; Nanotechnology ; Neurons - cytology ; NMR ; Nuclear magnetic resonance ; Pharmacology ; Protamines - administration & dosage ; Protamines - adverse effects ; Protamines - chemistry ; Radiography ; Rats ; Stem Cell Transplantation ; Stromal Cells - cytology ; T-Lymphocytes - cytology ; Usage
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8Varma, Nadimpalli Ravi S
9Arbab, Ali S
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descriptionWe 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.
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29Male
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31Microscopy, Electron
32Nanotechnology
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37Protamines - administration & dosage
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40Radiography
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titleSelf-assembling nanocomplexes by combining ferumoxytol, heparin and protamine for cell tracking by magnetic resonance imaging
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32Nanotechnology
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36Pharmacology
37Protamines - administration & dosage
38Protamines - adverse effects
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40Radiography
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43Stromal Cells - cytology
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abstractWe 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.
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