Heparin-coated superparamagnetic iron oxide for in vivo MR imaging of human MSCs
- Authors
- Lee, Ji-hye; Jung, Min Jin; Hwang, Yong Hwa; Lee, Young Jun; Lee, Seungsoo; Lee, Dong Yun; Shin, Heungsoo
- Issue Date
- Jun-2012
- Publisher
- ELSEVIER SCI LTD
- Keywords
- Stem cell; MRI (magnetic resonance imaging); Superparamagnetic iron oxide (SPIO); Heparin
- Citation
- BIOMATERIALS, v.33, no.19, pp.4861 - 4871
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOMATERIALS
- Volume
- 33
- Number
- 19
- Start Page
- 4861
- End Page
- 4871
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/165417
- DOI
- 10.1016/j.biomaterials.2012.03.035
- ISSN
- 0142-9612
- 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.
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