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
03/01/2012Pubmed ID
22366951Pubmed Central ID
PMC3296876DOI
10.1038/nm.2666Scopus ID
2-s2.0-84858004983 (requires institutional sign-in at Scopus site) 179 CitationsAbstract
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 JAAuthor
Matthew Budde PhD Associate Professor in the Neurosurgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
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
