In Vitro Characterization of Two Different Ultrasmall Iron Oxide Particles for Magnetic Resonance Cell Tracking

Fleige, Gerrit; Seeberger, Florian; Laux, Daniéla; Kresse, Mayk; Taupitz, Matthias; Pilgrimm, Herbert; Zimmer, Claus

doi:10.1097/00004424-200209000-00002

Cited by 98 publications

(58 citation statements)

References 28 publications

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“…[39][40][41][42][43][44] Earlier produced as VSOP-C184 (Ferropharm, Teltow, Germany), 45 these have been used for MSC labeling and found to have a detection limit of 40,000 cells in an 11.7 T MRI setting. 46 These NPs are no longer available.…”

Section: Introductionmentioning

confidence: 99%

Labeling of mesenchymal stem cells for MRI with single-cell sensitivity

Schellenberger¹,

Kratz²,

Farr³

et al. 2016

IJN

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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 single mesenchymal stem cells (MSC) by MRI. We achieved an average intracellular nanoparticle (NP) load of >10 pg 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 7 T 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 7 T 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.

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Section: Introductionmentioning

confidence: 99%

Labeling of mesenchymal stem cells for MRI with single-cell sensitivity

Schellenberger¹,

Kratz²,

Farr³

et al. 2016

IJN

Self Cite

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“…Iron particle incorporation by the cells causes a strong decrease in the transverse relaxation time, which results in signal loss in T2*-weighted MR imaging (Arbab et al, 2003;Bowen et al, 2002;Renshaw et al, 1986). No apparent long-term cytotoxic effects were observed after using the particles both in vitro and in vivo (Fleige et al, 2002;Stroh et al, 2004 and. For magnetic labeling sterile VSOP are added to the incubation medium.…”

Section: Concept 1: Cell Labeling For Mri-based Tracking In Vivo 41mentioning

confidence: 99%

Frameless Stereotaxy in Sheep - Neurosurgical and Imaging Techniques for Translational Stroke Research

Dreyer¹,

Stroh²,

Pösel³

et al. 2012

Advances in the Preclinical Study of Ischemic Stroke

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“…7 In addition, VSOP can reliably mark specific cells and assist in their subsequent detection in in vivo migration. [8][9][10] It was thus possible to monitor implanted VSOP-labeled neuronal progenitors over 6 weeks For that purpose, neutrophil granule cells and T cells were tagged with nanoparticles ex vivo, intravenously injected, and traced via MRI at inflammatory sites. [13][14][15] Although VSOP have been tested in clinical phase II trials, further assessment of cytotoxic effects is crucial.…”

Section: Introductionmentioning

confidence: 99%

“…However, after hippocampal slice preparation, microglia can diminish the amount of trauma-induced dead cells 10-fold within 7 days. 60 Thus, the increased PI signal can also be attributed to the absence of microglia and the deficient disposal of decaying cells (7)(8)(9). With regard to the exclusively SPIO-treated samples, VSOP-R1 significantly decreased viability in all regions of interest, whereas VSOP-R2 affected CA3 alone ( Figure 4S, T, and V).…”

mentioning

confidence: 97%

Biocompatibility of very small superparamagnetic iron oxide nanoparticles in murine organotypic hippocampal slice cultures and the role of microglia

Pohland

Glumm

Wiekhorst

et al. 2017

IJN

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Superparamagnetic iron oxide nanoparticles (SPIO) are applied as contrast media for magnetic resonance imaging (MRI) and treatment of neurologic diseases despite the fact that important information concerning their local interactions is still lacking. Due to their small size, SPIO have great potential for magnetically labeling different cell populations, facilitating their MRI tracking in vivo. Before SPIO are applied, however, their effect on cell viability and tissue homoeostasis should be studied thoroughly. We have previously published data showing how citrate-coated very small superparamagnetic iron oxide particles (VSOP) affect primary microglia and neuron cell cultures as well as neuron-glia cocultures. To extend our knowledge of VSOP interactions on the three-dimensional multicellular level, we further examined the influence of two types of coated VSOP (R1 and R2) on murine organotypic hippocampal slice cultures. Our data show that 1) VSOP can penetrate deep tissue layers, 2) long-term VSOP-R2 treatment alters cell viability within the dentate gyrus, 3) during short-term incubation VSOP-R1 and VSOP-R2 comparably modify hippocampal cell viability, 4) VSOP treatment does not affect cytokine homeostasis, 5) microglial depletion decreases VSOP uptake, and 6) microglial depletion plus VSOP treatment increases hippocampal cell death during short-term incubation. These results are in line with our previous findings in cell coculture experiments regarding microglial protection of neurite branching. Thus, we have not only clarified the interaction between VSOP, slice culture, and microglia to a degree but also demonstrated that our model is a promising approach for screening nanoparticles to exclude potential cytotoxic effects.

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In Vitro Characterization of Two Different Ultrasmall Iron Oxide Particles for Magnetic Resonance Cell Tracking

Abstract: Citrate-coated USPIO particles VSOP-C125 appear to have more favorable properties for magnetic labeling of macrophages than the carboxydextran-coated USPIO preparation DDM 43/34/103.

Cited by 98 publications

References 28 publications

Labeling of mesenchymal stem cells for MRI with single-cell sensitivity

Labeling of mesenchymal stem cells for MRI with single-cell sensitivity

Frameless Stereotaxy in Sheep - Neurosurgical and Imaging Techniques for Translational Stroke Research

Biocompatibility of very small superparamagnetic iron oxide nanoparticles in murine organotypic hippocampal slice cultures and the role of microglia

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