<i>In situ</i>
            labeling of immune cells with iron oxide particles: An approach to detect organ rejection by cellular MRI

Wu, Yijen; Ye, Qing; Foley, Lesley M.; Hitchens, T. Kevin; Sato, Kazuya; Williams, John B.; Ho, Chien

doi:10.1073/pnas.0507198103

Cited by 196 publications

(240 citation statements)

References 40 publications

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“…Furthermore, the niche environment that the stem cells exist in can be preserved. More interestingly, the distribution of cells in the olfactory bulb in response to different odor stimulations, or the ability to cause migratory deviations from the RMS in response to injury, should be amenable to study using these techniques, possibly to the point of detecting single cells (Shapiro et al, 2006;Wu et al, 2006;Heyn et al, 2006). The migratory pathway and endpoints can be readily co-registered with a wide variety of other anatomical and functional information available from MRI.…”

Section: Discussionmentioning

confidence: 99%

Magnetic resonance imaging of the migration of neuronal precursors generated in the adult rodent brain

et al. 2006

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Neural progenitor cells (NPCs) reside within the subventricular zone (SVZ) in rodents. These NPCs give rise to neural precursors in adults that migrate to the olfactory bulb (OB) along a welldefined pathway, the rostral migratory stream (RMS). Here we demonstrate that these NPCs can be labeled, in vivo, in adult rats with fluorescent, micron-sized iron oxide particles (MPIOs), and that magnetic resonance imaging (MRI) can detect migrating neural precursors carrying MPIOs along the RMS to the OB. Immunohistochemistry and electron microscopy indicated that particles were inside GFAP + neural progenitor cells in the SVZ, migrating PSA-NCAM + and Doublecortin + neural precursors within the RMS and OB, and Neu-N + mature neurons in the OB. This work demonstrates that in vivo cell labeling of progenitor cells for MRI is possible and enables the serial, non-invasive visualization of endogenous progenitor/precursor cell migration.

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Section: Discussionmentioning

confidence: 99%

Magnetic resonance imaging of the migration of neuronal precursors generated in the adult rodent brain

et al. 2006

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“…Second, our model assumes that the average contrast over a region of interest is comprised of numerous voxels. However, when certain cellular CAs, such as micron-sized SPIO agents (5,22), are used, in vivo contrast may be highly localized and punctate. This may offer improved detectability, and the contrast model may underestimate contrast in these cases.…”

Section: Discussionmentioning

confidence: 99%

“…SPIO particles with surfaces conjugated to targeting entities, such as peptides or antibodies, have also been described (4). Intracellular applications of SPIO for cell-tracking in animal models is a rapidly evolving research area (5), and the clinical translation of these techniques is already in the early stage (6).…”

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confidence: 99%

Theoretical MRI contrast model for exogenous T₂ agents

Mills

Ahrens

2007

Magnetic Resonance in Med

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The rational development of new generations of MRI contrast agents (CAs) requires a scheme for predicting contrast enhancement. Previous contrast predictions have been based largely on empirical results in specific systems. Here we present a general theoretical model for evaluating the minimum concentration of T 2 CA required for satisfactory image contrast. This analytic contrast model is applicable to a wide range of T 2 -type agents and delivery scenarios, and requires only a few readily evaluated parameters. We demonstrated the model by predicting contrast produced by superparamagnetic ferumoxide and the iron storage protein, ferritin. We then experimentally verified the predictions using suspensions of Feridexா and ferritin in phantoms. The model was also used to compare the contrast efficacy of the metal ions in two clinically approved T 1 -and T 2 -type CAs. In the Appendix we present a numerical formalism that is useful for relating image contrast and agent concentration when gradient-echo (GRE) T* 2 -weighted (T There is great interest in developing new generations of MRI contrast agents (CAs) that can be used for diagnostic purposes, therapeutic monitoring, and to further our understanding of diseases. New generations of agents can often provide MRI contrast for specific cell types, detect the presence of specific molecules, such as enzymes and nucleic acids (1-3), and be responsive to physiology.Superparamagnetic iron oxide (SPIO) CAs are widely used as a platform for many of these emerging cellularmolecular applications (1). SPIO agents typically consist of an iron-oxide nanocrystal that is coated with dextran or polymer and have a net median diameter of 10 -100 nm. SPIO particles perturb the static magnetic field out to a distance on the order of ϳ50 2 times its diameter, resulting in a dramatic reduction in T 2 of nearby water molecules. The resulting images exhibit hypointense regions, indicating agent accumulation. Unmodified SPIO particles, such as Resovist, Feridex, and Combidex, have been used for cellular imaging (4) and are FDA-approved for detecting liver lesions and distinguishing between normal and cancerous lymph nodes. SPIO particles with surfaces conjugated to targeting entities, such as peptides or antibodies, have also been described (4). Intracellular applications of SPIO for cell-tracking in animal models is a rapidly evolving research area (5), and the clinical translation of these techniques is already in the early stage (6).In addition, T 2 -type CAs are included in a new category of intracellular labeling approaches that utilize genetically-encoded metalloproteins (2,7). In this approach, metalloproteins from the ferritin family are expressed in specific host tissues. These iron-storage metalloproteins effectively become a superparamagnetic CA by sequestering endogenous iron from the organism and thus imparting MRI contrast to targeted tissues.For useful images to be generated, CAs must accumulate in cells or tissues in adequate concentrations. Moreover, too high of a concentra...

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“…Thus, it serves as an effective cellular system for innate immune response evaluation. Recent reports mainly focused on labeling monocyte cells with NPs for therapeutic imaging (Settles, et al, 2011;Von zur Muhlen et al, 2010;Wu et al, 2006), and only a few reports demonstrated the proinflammatory effects of iron oxide NPs on human monocyte cell lines (Laskar et al, 2012;Zhu et al, 2011). Further understanding of the interactions between NPs and human monocyte cell line will be beneficial for predicting NP-induced inflammatory responses, and provide valuable information for NP design to achieve alleviated inflammation in biological systems.…”

Section: Introductionmentioning

confidence: 99%

The responses of immune cells to iron oxide nanoparticles

Sherwood

Lackey

et al. 2016

J of Applied Toxicology

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Immune cells play an important role in recognizing and removing foreign objects, such as nanoparticles. Among various parameters, surface coatings of nanoparticles are the first contact with biological system, which critically affect nanoparticle interactions. Here, surface coating effects on nanoparticle cellular uptake, toxicity and ability to trigger immune response were evaluated on a human monocyte cell line using iron oxide nanoparticles. The cells were treated with nanoparticles of three types of coatings (negatively charged polyacrylic acid, positively charged polyethylenimine and neutral polyethylene glycol). The cells were treated at various nanoparticle concentrations (5, 10, 20, 30, 50 μg ml À1 or 2, 4, 8, 12, 20 μg cm À2 ) with 6 h incubation or treated at a nanoparticle concentration of 50 μg ml À1 (20 μg cm À2 ) at different incubation times (6, 12, 24, 48 or 72 h). Cell viability over 80% was observed for all nanoparticle treatment experiments, regardless of surface coatings, nanoparticle concentrations and incubation times. The much lower cell viability for cells treated with free ligands (e.g.~10% for polyethylenimine) suggested that the surface coatings were tightly attached to the nanoparticle surfaces. The immune responses of cells to nanoparticles were evaluated by quantifying the expression of toll-like receptor 2 and tumor necrosis factor-α. The expression of tumor necrosis factor-α and toll-like receptor 2 were not significant in any case of the surface coatings, nanoparticle concentrations and incubation times. These results provide useful information to select nanoparticle surface coatings for biological and biomedical applications.

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In situ labeling of immune cells with iron oxide particles: An approach to detect organ rejection by cellular MRI

Cited by 196 publications

References 40 publications

Magnetic resonance imaging of the migration of neuronal precursors generated in the adult rodent brain

Magnetic resonance imaging of the migration of neuronal precursors generated in the adult rodent brain

Theoretical MRI contrast model for exogenous T₂ agents

The responses of immune cells to iron oxide nanoparticles

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In situ labeling of immune cells with iron oxide particles: An approach to detect organ rejection by cellular MRI

Cited by 196 publications

References 40 publications

Magnetic resonance imaging of the migration of neuronal precursors generated in the adult rodent brain

Magnetic resonance imaging of the migration of neuronal precursors generated in the adult rodent brain

Theoretical MRI contrast model for exogenous T2 agents

The responses of immune cells to iron oxide nanoparticles

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Theoretical MRI contrast model for exogenous T₂ agents