title: Highly efficient magnetic stem cell labeling with citrate-coated superparamagnetic iron oxide nanoparticles for MRI tracking.
abstract: Tracking of transplanted stem cells is essential to monitor safety and efficiency of cell-based therapies. Magnetic resonance imaging (MRI) offers a very sensitive, repetitive and non-invasive in vivo detection of magnetically labeled cells but labeling with commercial superparamagnetic iron oxide nanoparticles (SPIONs) is still problematic because of low labeling efficiencies and the need of potentially toxic transfection agents. In this study, new experimental citrate-coated SPIONs and commercial Endorem and Resovist SPIONs were investigated comparatively in terms of in vitro labeling efficiency, effects on stem cell functionality and in vivo MRI visualization. Efficient labeling of human mesenchymal stem cells (MSCs) without transfection agents was only achieved with Citrate SPIONs. Magnetic labeling of human MSCs did not affect cell proliferation, presentation of typical cell surface marker antigens and differentiation into the adipogenic and osteogenic lineages. However, chondrogenic differentiation and chemotaxis were significantly impaired with increasing SPION incorporation. Transplanted SPION-labeled MSCs were visualized in vivo after intramuscular injection in rats by 7T-MRI and were retrieved ex vivo by Prussian Blue and immunohistochemical stainings. Though a careful titration of SPION incorporation, cellular function and MRI visualization is essential, Citrate SPIONs are very efficient intracellular magnetic labels for in vivo stem cell tracking by MRI.
authors.affiliation: Tissue Engineering Laboratory and Berlin-Brandenburg Center for Regenerative Therapies, Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. kristin.andreas@charite.de
authors.forename: Kristin
authors.initials: K
authors.lastname: Andreas
authors.forename: Radostina
authors.initials: R
authors.lastname: Georgieva
authors.forename: Mechthild
authors.initials: M
authors.lastname: Ladwig
authors.forename: Susanne
authors.initials: S
authors.lastname: Mueller
authors.forename: Michael
authors.initials: M
authors.lastname: Notter
authors.forename: Michael
authors.initials: M
authors.lastname: Sittinger
authors.forename: Jochen
authors.initials: J
authors.lastname: Ringe
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D019343:Citric Acid / Q000737:chemistry*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000737:chemistry* / Q000166:cytology*; D051381:Rats
chemical_list: D058185:Magnetite Nanoparticles; D019343:Citric Acid