title: Self-assembling nanocomplexes by combining ferumoxytol, heparin and protamine for cell tracking by magnetic resonance imaging.
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.
authors.affiliation: Frank Laboratory and Laboratory of Diagnostic Radiology Research, Department of Radiology and Imaging Sciences, US National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Mya S
authors.initials: MS
authors.lastname: Thu
authors.forename: L Henry
authors.initials: LH
authors.lastname: Bryant
authors.forename: Tiziana
authors.initials: T
authors.lastname: Coppola
authors.forename: E Kay
authors.initials: EK
authors.lastname: Jordan
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Budde
authors.forename: Bobbi K
authors.initials: BK
authors.lastname: Lewis
authors.forename: Aneeka
authors.initials: A
authors.lastname: Chaudhry
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Ren
authors.forename: Nadimpalli Ravi S
authors.initials: NR
authors.lastname: Varma
authors.forename: Ali S
authors.initials: AS
authors.lastname: Arbab
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Frank
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology; D001921:Brain / Q000166:cytology* / Q000000981:diagnostic imaging / Q000648:ultrastructure; D002454:Cell Differentiation / Q000187:drug effects; D058948:Cell Tracking / Q000379:methods*; D002986:Clinical Trials as Topic; D016895:Culture Media, Serum-Free; D011992:Endosomes / Q000648:ultrastructure; D052203:Ferrosoferric Oxide / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D006801:Humans; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects* / Q000737:chemistry* / Q000648:ultrastructure; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008854:Microscopy, Electron; D009474:Neurons / Q000166:cytology; D011479:Protamines / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D011859:Radiography; D051381:Rats; D033581:Stem Cell Transplantation; D017154:Stromal Cells / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology
chemical_list: D016895:Culture Media, Serum-Free; D058185:Magnetite Nanoparticles; D011479:Protamines; D006493:Heparin; D052203:Ferrosoferric Oxide