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Amine‐surface‐modified superparamagnetic iron oxide nanoparticles interfere with differentiation of human mesenchymal stem cells
Authors:You‐Kang Chang  Yu‐Peng Liu  Jennifer H. Ho  Shu‐Ching Hsu  Oscar K. Lee
Affiliation:1. Institute of Clinical Medicine, National Yang‐Ming University, Taipei, Taiwan;2. Department of Radiation Oncology, Buddhist Tzu Chi General Hospital, Taipei Branch, New Taipei City, Taiwan;3. School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan;4. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan;5. Center for Stem Cell Research, Taipei Medical University‐Wan Fang Medical Center, Taipei, Taiwan;6. Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan;7. Department of Ophthalmology, Taipei Medical University‐Wan Fang Medical Center, Taipei, Taiwan;8. National Institute of Infectious Disease and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan;9. Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan, Taipei, Taiwan;10. Stem Cell Research Center, National Yang‐Ming University, Taipei, Taiwan
Abstract:Superparamagnetic iron oxide (SPIO) nanoparticles have been widely used for stem cell labeling and tracking. Surface modification has been known to improve biocompatibility, biodistribution, and labeling efficiency of SPIO nanoparticles. However, the effects of amine (NHurn:x-wiley:07360266:media:JOR22088:tex2gif-stack-1)‐surface‐modified SPIO nanoparticles on proliferation and differentiation of human mesenchymal stem cells (hMSCs) remain unclear. The purpose of this study is to investigate how amine‐surface‐modified SPIO nanoparticles affected hMSCs. In this study, intracellular uptake and the contiguous presence of amine‐surface‐modified SPIO nanoparticles in hMSCs were demonstrated by Prussian blue staining, transmission electron microscopy and magnetic resonance imaging. Moreover, accelerated cell proliferation was found to be associated with cellular internalization of amine‐surface‐modified SPIO nanoparticles. The osteogenic and chondrogenic differentiation potentials of hMSCs were impaired after treating with SPIO, while adipogenic potential was relatively unaffected. Altered cytokine production profile in hMSCs caused by amine‐surface‐modified SPIO nanoparticles may account for the increased proliferation and impaired differentiation potentials; concentrations of the growth factors in the SPIO‐labeled condition medium including amphiregulin, glial cell‐derived neurotrophic factor, heparin‐binding EGF‐like growth factor and vascular endothelial growth factor, as well as soluble form of macrophage colony‐stimulating factor receptor and SCF receptor, were higher than in the unlabeled‐condition medium. In summary, although amine‐surface‐modified SPIO labeling is effective for cell tracking, properties of hMSCs may alter as a consequence and this needs to be taken into account when evaluating therapeutic efficacies of SPIO‐labeled stem cells in vivo. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1499–1506, 2012
Keywords:mesenchymal stem cells  superparamagnetic iron oxide  nanoparticles  multilineage differentiation
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