The role of nanoparticle concentration-dependent induction of cellular stress in the internalization of non-toxic cationic magnetoliposomes

Soenen, Stefaan J.; Illyés, Eszter; Vercauteren, Dries; Braeckmans, Kevin; Májer, Zsuzsa; Smedt, Stefaan C. De; Cuyper, Marcel De

doi:10.1016/j.biomaterials.2009.08.050

Cited by 106 publications

(70 citation statements)

References 38 publications

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“…5). T 2 *-weighted imaging revealed strong negative contrast in areas of labeled hESC-CPC injection (R2* value, 0.34 6 0.096 ms 21 and 0.29 6 0.04 ms…”

Section: Ferumoxytol-labeled Cells Can Be Detected In Tissue Ex Vivomentioning

confidence: 99%

“…Superparamagnetic iron oxide nanoparticles (SPIOs) are well characterized and widely used cell-labeling agents for magnetic resonance imaging (MRI) [15][16][17]. However, SPIO exposure has been associated with cytotoxicity, actin-cytoskeleton modulation, and carcinogenesis, which are undesirable side effects when labeling hESC-derived cardiac cells [18][19][20][21][22]. 19 F) labeling might be a promising alternative for cell imaging, because it has little effect on stem cell viability, proliferation, and differentiation [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

“…1B, 1C; supplemental online Table 1). Higher doses of ferumoxytol did not significantly increase the R2* values (ms 21 ; p . .05) in hESC-CPCs (Fig.…”

Section: Variation In Signal Intensity Is Dependent On Ferumoxytol Exmentioning

confidence: 99%

“…5; supplemental online Video 3). Unlabeled hESC-CPCs were indistinguishable from surrounding tissue (R2* value, 0.018 6 0.002 ms 21 and 0.020 6 0.001 ms…”

mentioning

confidence: 98%

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Magnetic Resonance Imaging of Iron Oxide-Labeled Human Embryonic Stem Cell-Derived Cardiac Progenitors

Skelton

Khoja

Almeida

et al. 2015

Stem Cells Translational Medicine

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Given the limited regenerative capacity of the heart, cellular therapy with stem cell-derived cardiac cells could be a potential treatment for patients with heart disease. However, reliable imaging techniques to longitudinally assess engraftment of the transplanted cells are scant. To address this issue, we used ferumoxytol as a labeling agent of human embryonic stem cell-derived cardiac progenitor cells (hESC-CPCs) to facilitate tracking by magnetic resonance imaging (MRI) in a large animal model. Differentiating hESCs were exposed to ferumoxytol at different time points and varying concentrations. We determined that treatment with ferumoxytol at 300 mg/ml on day 0 of cardiac differentiation offered adequate cell viability and signal intensity for MRI detection without compromising further differentiation into definitive cardiac lineages. Labeled hESC-CPCs were transplanted by open surgical methods into the left ventricular free wall of uninjured pig hearts and imaged both ex vivo and in vivo. Comprehensive T 2 *-weighted images were obtained immediately after transplantation and 40 days later before termination. The localization and dispersion of labeled cells could be effectively imaged and tracked at days 0 and 40 by MRI. Thus, under the described conditions, ferumoxytol can be used as a long-term, differentiation-neutral cell-labeling agent to track transplanted hESC-CPCs in vivo using MRI. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:67-74 SIGNIFICANCEThe development of a safe and reproducible in vivo imaging technique to track the fate of transplanted human embryonic stem cell-derived cardiac progenitor cells (hESC-CPCs) is a necessary step to clinical translation. An iron oxide nanoparticle (ferumoxytol)-based approach was used for cell labeling and subsequent in vivo magnetic resonance imaging monitoring of hESC-CPCs transplanted into uninjured pig hearts. The present results demonstrate the use of ferumoxytol labeling and imaging techniques in tracking the location and dispersion of cell grafts, highlighting its utility in future cardiac stem cell therapy trials.

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“…5). T 2 *-weighted imaging revealed strong negative contrast in areas of labeled hESC-CPC injection (R2* value, 0.34 6 0.096 ms 21 and 0.29 6 0.04 ms…”

Section: Ferumoxytol-labeled Cells Can Be Detected In Tissue Ex Vivomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…1B, 1C; supplemental online Table 1). Higher doses of ferumoxytol did not significantly increase the R2* values (ms 21 ; p . .05) in hESC-CPCs (Fig.…”

Section: Variation In Signal Intensity Is Dependent On Ferumoxytol Exmentioning

confidence: 99%

“…5; supplemental online Video 3). Unlabeled hESC-CPCs were indistinguishable from surrounding tissue (R2* value, 0.018 6 0.002 ms 21 and 0.020 6 0.001 ms…”

mentioning

confidence: 98%

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Magnetic Resonance Imaging of Iron Oxide-Labeled Human Embryonic Stem Cell-Derived Cardiac Progenitors

Skelton

Khoja

Almeida

et al. 2015

Stem Cells Translational Medicine

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“…11,[20][21][22][23][24][25] In contrast, Soenen et al showed that high intracellular concentrations of SPIO limited the proliferation capacity of murine fibroblasts and neural progenitor cells via impaired actin-mediated signaling of cytoskeletal changes. 26,27 Previously, we published data on the promotion of neurite outgrowth using a high concentration of VSOP-R2 in neuronglia cocultures in contrast to the degeneration of neurons after VSOP exposure in neuronal cell cultures. 28 After obtaining this significant information on VSOP interaction using primary cell cultures and primary cell cocultures, we analyzed the particle and cell type-induced effects caused by VSOP treatment within a more complex setup of organotypic hippocampal slice culture (OHSC).…”

Section: Introductionmentioning

confidence: 99%

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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Nanoparticles for Stem‐Cell Engineering

Jabbari

2015

Stem‐Cell Nanoengineering

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The role of nanoparticle concentration-dependent induction of cellular stress in the internalization of non-toxic cationic magnetoliposomes

Cited by 106 publications

References 38 publications

Magnetic Resonance Imaging of Iron Oxide-Labeled Human Embryonic Stem Cell-Derived Cardiac Progenitors

Magnetic Resonance Imaging of Iron Oxide-Labeled Human Embryonic Stem Cell-Derived Cardiac Progenitors

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

Nanoparticles for Stem‐Cell Engineering

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