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
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