title: Heparin-coated superparamagnetic iron oxide for in vivo MR imaging of human MSCs.
abstract: Human mesenchymal stem cells (hMSCs) offer significant therapeutic potential in the field of regenerative medicine and high-resolution magnetic resonance imaging (MRI) is useful modality to visualize in vivo kinetics of transplanted stem cells. For successful MR imaging, there is a great need for effective contrast agents for stem cell labeling with high uptake yield and low toxicity. Here, we present superparamagnetic iron oxide (SPIO) nanoparticles coated with unfractionated heparin (UFH-SPIO) as a new negative contrast agent for in vivo MR imaging of hMSCs. The uptake of UFH-SPIO by hMSCs was effective without the aid of transfection agents, which was dependent on the concentration and exposure time. The uptake efficiency of UFH-SPIO was greater than that of DEX-SPIO (SPIO coated with dextran) by approximately 3 folds when treated for 1 h. TEM and Prussian blue staining confirmed that UFH-SPIO nanoparticles were internalized into the cytosol of hMSCs which existed during in vitro subculture for 28 days. Low temperature endocytosis inhibition assay demonstrated that the incorporation of UFH-SPIO into hMSCs was likely to be mediated by endocytosis. When the phantom of UFH-SPIO-labeled hMSCs was visualized with 3-T T(2)-weighted MRI, the hypointensity signals of UFH-SPIO-labeled hMSCs were linearly correlated with the concentration of the nanoparticles. The cellular labeling using UFH-SPIO did not reduce the viability, proliferation or differentiation potential to osteogenic and adipogenic lineages of hMSCs. When the UFH-SPIO-labeled hMSCs were transplanted into the left renal subcapsular membranes of nude mice, they were successfully visualized and detected by T(2) and T(2)(∗)-weighted MRI for a month. Collectively, these results suggest that UFH-SPIO nanoparticles are promising as a new MRI contrast agent for in vivo long-term tracking of hMSCs.
authors.affiliation: Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Ji-hye
authors.initials: JH
authors.lastname: Lee
authors.forename: Min Jin
authors.initials: MJ
authors.lastname: Jung
authors.forename: Yong Hwa
authors.initials: YH
authors.lastname: Hwang
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Lee
authors.forename: Seungsoo
authors.initials: S
authors.lastname: Lee
authors.forename: Dong Yun
authors.initials: DY
authors.lastname: Lee
authors.forename: Heungsoo
authors.initials: H
authors.lastname: Shin
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D003287:Contrast Media / Q000737:chemistry*; D003911:Dextrans / Q000737:chemistry*; D006367:HeLa Cells; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008819:Mice, Nude
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D006493:Heparin; C065507:ferumoxides