Medical College of Wisconsin
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Self-assembling nanocomplexes by combining ferumoxytol, heparin and protamine for cell tracking by magnetic resonance imaging. Nat Med 2012 Feb 26;18(3):463-7

Date

03/01/2012

Pubmed ID

22366951

Pubmed Central ID

PMC3296876

DOI

10.1038/nm.2666

Scopus ID

2-s2.0-84858004983   136 Citations

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.

Author List

Thu MS, Bryant LH, Coppola T, Jordan EK, Budde MD, Lewis BK, Chaudhry A, Ren J, Varma NR, Arbab AS, Frank JA

Author

Matthew Budde PhD Associate Professor in the Neurosurgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis
Bone Marrow Cells
Brain
Cell Differentiation
Cell Tracking
Clinical Trials as Topic
Culture Media, Serum-Free
Endosomes
Ferrosoferric Oxide
Hematopoietic Stem Cells
Heparin
Humans
Magnetic Resonance Imaging
Magnetite Nanoparticles
Male
Microscopy, Electron
Neurons
Protamines
Radiography
Rats
Stem Cell Transplantation
Stromal Cells
T-Lymphocytes
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