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Blood, 15 August 2004, Vol. 104, No. 4, pp. 1217-1223.
Prepublished online as a Blood First Edition Paper on April 20, 2004; DOI 10.1182/blood-2004-02-0655.


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Submitted February 23, 2004
Accepted April 9, 2004

Efficient Magnetic Cell Labeling with Protamine Sulfate Complexed to Ferumoxides for Cellular MRI

Ali S Arbab*, Gene T Yocum, Heather Kalish, Elaine K Jordan, Stasia A Anderson, Aarif Y Khakoo, Elizabeth J Read, and Joseph A Frank

Laboratory of Diagnostic Radiology Research, National Institutes of Health, Bethesda, Maryland, USA
NINDS, National Institutes of Health, Bethesda, Maryland, USA
NHLBI, National Institutes of Health, Bethesda, Maryland, USA
Department of Transfusion Medicine, National Institutes of Health, Bethesda, Maryland, USA

* Corresponding author; email: saali{at}cc.nih.gov.

Recently, there have been several reports using various superparamagnetic iron oxide (SPIO) nanoparticles to label mammalian cells for monitoring their temporal and spatial migration in vivo by magnetic resonance imaging (MRI). The purpose of this study was to evaluate the efficiency and toxicity of labeling cells using two commercially available FDA-approved agents, ferumoxides, a suspension of dextran-coated SPIO used as an MRI contrast agent, and protamine sulfate, conventionally used to reverse heparin anticoagulation but also used ex vivo as a cationic transfection agent. After labeling of human mesenchymal (MSC) and hematopoietic (CD 34+) stem cells and other mammalian cells with ferumoxides-protamine sulfate complexes (FE-Pro), cellular toxicity, functional capacity and quantitative cellular iron incorporation were determined. FE-Pro labeled cells demonstrated no short or long-term toxicity, changes in differentiation capacity of the stem cells, or changes in phenotype, when compared to unlabeled cells. Efficient labeling with FE-Pro was observed with iron content per cell varying between 2.01 ± 0.1 picograms for CD 34+ cells and 10.94 ± 1.86 picograms for MSC with 100% of cells labeled. Cell labeling using these agents should facilitate the translation of this method to clinical trials for evaluation of trafficking of infused or transplanted cells by MRI.


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Related Article in Blood Online:

MR-based cellular imaging: ready for prime time?
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Blood 2004 104: 916-917. [Full Text] [PDF]

Related Letter in Blood Online:

Chondrogenic differentiation of mesenchymal stem cells is inhibited after magnetic labeling with ferumoxides
Jeff W. M. Bulte, Dara L. Kraitchman, Alastair M. Mackay, Mark F. Pittenger, Ali S. Arbab, Gene T. Yocum, Heather Kalish, Elaine K. Jordan, Stasia A. Anderson, Aarif Y. Khakoo, Elizabeth J. Read, and Joseph A. Frank
Blood 2004 104: 3410-3413. [Full Text] [PDF]



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