Highly efficient magnetic stem cell labeling with citrate-coated superparamagnetic iron oxide nanoparticles for MRI tracking

Andreas, Kristin; Georgieva, Radostina; Ladwig, Mechthild; Mueller, Susanne; Notter, Michael; Sittinger, Michael; Ringe, Jochen

doi:10.1016/j.biomaterials.2012.02.064

Cited by 204 publications

(139 citation statements)

References 53 publications

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“…To the best of our knowledge, the most sensitive MRI detection has been accomplished for 1,000 ferumoxytol-labeled cells after intracerebral implantation when cells were labeled with 2.2 pg Fe per cell. [27][28][29][30] However, no attempts have been made to visualize single cells with any of these approaches. Alternatively, Bulte 31 proposed in vivo labeling of MSC obtained by bone marrow (BM) aspiration from rats after prior IV injection with ferumoxytol.…”

Section: Introductionmentioning

confidence: 99%

“…17 More recently, the cellular uptake of 69.1 pg Fe per hMSC (human MSC) has been reported for citrate-coated superparamagnetic iron oxide nanoparticles from MagneticFluids (Berlin, Germany). 27 Although many studies have investigated MSC labeling for MRI, the results are difficult to compare due to the wide range of NPs and methodologies used to label cells. 14,[33][34][35] One of the most commonly used methods to enhance NP uptake by nonphagocytic cells is to use polycationic transfection agents (TAs) such as protamine sulfate (PS) (FDA approved) to form positively charged NP complexes, which penetrate cell membranes more easily.…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Introductionmentioning

confidence: 99%

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

Schellenberger¹,

Kratz²,

Farr³

et al. 2016

IJN

View full text Add to dashboard Cite

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“…To date, most published techniques have employed passive internalization of MNPs via endocytosis, which allows for effective magnetic modification of cells [11][12][13]. However, uptake of MNPs by cells entails several major drawbacks, such as (1) a lengthy internalization process, requiring up to 72 h of co-incubation of MNPs with cells [14,15] and (2) potential toxic effects of early-stage cytoplasminternalized nanoparticles [16].…”

Section: Introductionmentioning

confidence: 99%

Cell surface engineering with polyelectrolyte-stabilized magnetic nanoparticles: A facile approach for fabrication of artificial multicellular tissue-mimicking clusters

et al. 2015

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Regenerative medicine requires new ways to assemble and manipulate cells for fabrication of tissue-like constructs. Here we report a novel approach for cell surface engineering of human cells using polymer-stabilized magnetic nanoparticles (MNPs). Cationic polyelectrolyte-coated MNPs are directly deposited onto cellular membranes, producing a mesoporous semi-permeable layer and rendering cells magnetically responsive. Deposition of MNPs can be completed within minutes, under cell-friendly conditions (room temperature and physiologic media). Microscopy (TEM, SEM, AFM, and enhanced dark-field imaging) revealed the intercalation of nanoparticles into the cellular microvilli network. A detailed viability investigation was performed and suggested that MNPs do not inhibit membrane integrity, enzymatic activity, adhesion, proliferation, or cytoskeleton formation, and do not induce apoptosis in either cancer or primary cells. Finally, magnetically functionalized cells were employed to fabricate viable layered planar (two-cell layers) cell sheets and 3D multicellular spheroids.

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“…2,3 SPIOs have been optimized to label single cells in vitro and subsequently to visualize tissue alterations or disease progression in vivo. [4][5][6][7] In addition, SPIOs serve as carriers for targeted drug delivery or in cancer treatment with magnetic hyperthermia. [8][9][10] However, the application of nanoparticles, in particular under disease conditions, raises the important question of how they may potentially cause adverse effects or influence the cell vitality after entering the central nervous system (CNS).…”

Section: Introductionmentioning

confidence: 99%

“…67,68 In addition, the negatively charged carboxyl groups of ferucarbotran enhance particle uptake at higher particle concentrations. 7,69 However, cellular uptake of VSOPs appeared to be much faster and quantitatively superior compared to polymercoated nanoparticles, probably due to their small size (around 7 nm), higher surface-to-volume ratio, and binding to extracellular membrane glycosaminoglycans prior to internalization. 30,38,70 On the one hand, citrate-coated particles have been shown to be incorporated by repulsive interaction with the cell membrane, and are subsequently highly concentrated in the cytoplasm.…”

mentioning

confidence: 99%

New findings about iron oxide nanoparticles and their different effects on murine primary brain cells

Neubert¹,

Wagner²,

Kiwit³

et al. 2015

IJN

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The physicochemical properties of superparamagnetic iron oxide nanoparticles (SPIOs) enable their application in the diagnostics and therapy of central nervous system diseases. However, since crucial information regarding side effects of particle–cell interactions within the central nervous system is still lacking, we investigated the influence of novel very small iron oxide particles or the clinically approved ferucarbotran or ferumoxytol on the vitality and morphology of brain cells. We exposed primary cell cultures of microglia and hippocampal neurons, as well as neuron–glia cocultures to varying concentrations of SPIOs for 6 and/or 24 hours, respectively. Here, we show that SPIO accumulation by microglia and subsequent morphological alterations strongly depend on the respective nanoparticle type. Microglial viability was severely compromised by high SPIO concentrations, except in the case of ferumoxytol. While ferumoxytol did not cause immediate microglial death, it induced severe morphological alterations and increased degeneration of primary neurons. Additionally, primary neurons clearly degenerated after very small iron oxide particle and ferucarbotran exposure. In neuron–glia cocultures, SPIOs rather stimulated the outgrowth of neuronal processes in a concentration- and particle-dependent manner. We conclude that the influence of SPIOs on brain cells not only depends on the particle type but also on the physiological system they are applied to.

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Highly efficient magnetic stem cell labeling with citrate-coated superparamagnetic iron oxide nanoparticles for MRI tracking

Cited by 204 publications

References 53 publications

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

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

Cell surface engineering with polyelectrolyte-stabilized magnetic nanoparticles: A facile approach for fabrication of artificial multicellular tissue-mimicking clusters

New findings about iron oxide nanoparticles and their different effects on murine primary brain cells

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Highly efficient magnetic stem cell labeling with citrate-coated superparamagnetic iron oxide nanoparticles for MRI tracking

Cited by 204 publications

References 53 publications

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

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

Cell surface engineering with polyelectrolyte-stabilized magnetic nanoparticles: A facile approach for fabrication of artificial multicellular tissue-mimicking clusters

New findings about iron oxide nanoparticles and&nbsp;their different effects on murine primary brain cells

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New findings about iron oxide nanoparticles and their different effects on murine primary brain cells