Labeling of mesenchymal stem cells for MRI with single-cell sensitivity
Autor: | Matthias Taupitz, Susanne Wagner, Eyk Schellenberger, Norbert Loewa, Joerg Schnorr, Angela Ariza de Schellenberger, Ralf Hauptmann, Harald Kratz, Tracy D. Farr |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Materials science Population Biophysics Contrast Media Pharmaceutical Science Bioengineering 02 engineering and technology 600 Technik Medizin angewandte Wissenschaften::610 Medizin und Gesundheit Biomaterials Mice 03 medical and health sciences chemistry.chemical_compound Magnetic particle imaging Nuclear magnetic resonance Single-cell analysis International Journal of Nanomedicine In vivo Drug Discovery medicine Animals Magnetite Nanoparticles education VSOP Cells Cultured Resovist® Original Research mesenchymal stem cells education.field_of_study medicine.diagnostic_test Phantoms Imaging Organic Chemistry Mesenchymal stem cell Dextrans Magnetic resonance imaging General Medicine 021001 nanoscience & nanotechnology Magnetic Resonance Imaging magnetic field microdistortions Mice Inbred C57BL 030104 developmental biology chemistry MCP Single-Cell Analysis single-cell imaging 0210 nano-technology Iron oxide nanoparticles |
Zdroj: | International Journal of Nanomedicine |
DOI: | 10.17169/refubium-21244 |
Popis: | Angela Ariza de Schellenberger,1 Harald Kratz,1 Tracy D Farr,2,3 Norbert Löwa,4 Ralf Hauptmann,1 Susanne Wagner,1 Matthias Taupitz,1 Jörg Schnorr,1 Eyk A Schellenberger1 1Department of Radiology, 2Department of Experimental Neurology, Center for Stroke Research Berlin, Charité – Universitätsmedizin Berlin, Berlin, Germany; 3School of Life Sciences, University of Nottingham, Medical School, Nottingham, UK; 4Department of Biomagnetic Signals, Physikalisch-Technische Bundesanstalt Berlin, Berlin, Germany Abstract: Sensitive cell detection by magnetic resonance imaging (MRI) is an important tool for the development of cell therapies. However, clinically approved contrast agents that allow single-cell detection are currently not available. Therefore, we compared very small iron oxide nanoparticles (VSOP) and new multicore carboxymethyl dextran-coated iron oxide nanoparticles (multicore particles, MCP) designed by our department for magnetic particle imaging (MPI) with discontinued Resovist® regarding their suitability for detection of singlemesenchymal stem cells (MSC) by MRI. We achieved an average intracellular nanoparticle (NP) load of>10pg Fe per cell without the use of transfection agents. NP loading did not lead to significantly different results in proliferation, colony formation, and multilineage in vitro differentiation assays in comparison to controls. MRI allowed single-cell detection using VSOP, MCP, and Resovist® in conjunction with high-resolution T2*-weighted imaging at 7T with postprocessing of phase images in agarose cell phantoms and in vivo after delivery of 2,000 NP-labeled MSC into mouse brains via the left carotid artery. With optimized labeling conditions, a detection rate of ~45% was achieved; however, the experiments were limited by nonhomogeneous NP loading of the MSC population. Attempts should be made to achieve better cell separation for homogeneous NP loading and to thus improve NP-uptake-dependent biocompatibility studies and cell detection by MRI and future MPI. Additionally, using a 7T MR imager equipped with a cryocoil resulted in approximately two times higher detection. In conclusion, we established labeling conditions for new high-relaxivity MCP, VSOP, and Resovist® for improved MRI of MSC with single-cell sensitivity. Keywords: magnetic field microdistortions, single-cell imaging, mesenchymal stem cells, VSOP, MCP, Resovist® |
Databáze: | OpenAIRE |
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