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Cellular Transfer of Magnetic Nanoparticles Via Cell Microvesicles: Impact on Cell Tracking by Magnetic Resonance Imaging

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ABSTRACT

Purpose

Cell labeling with magnetic nanoparticles can be used to monitor the fate of transplanted cells in vivo by magnetic resonance imaging. However, nanoparticles initially internalized in administered cells might end up in other cells of the host organism. We investigated a mechanism of intercellular cross-transfer of magnetic nanoparticles to different types of recipient cells via cell microvesicles released under cellular stress.

Methods

Three cell types (mesenchymal stem cells, endothelial cells and macrophages) were labeled with 8-nm iron oxide nanoparticles. Then cells underwent starvation stress, during which they produced microvesicles that were subsequently transferred to unlabeled recipient cells.

Results

The analysis of the magnetophoretic mobility of donor cells indicated that magnetic load was partially lost under cell stress. Microvesicles shed by stressed cells participated in the release of magnetic label. Moreover, such microvesicles were uptaken by naïve cells, resulting in cellular redistribution of nanoparticles. Iron load of recipient cells allowed their detection by MRI.

Conclusions

Cell microvesicles released under stress may be disseminated throughout the organism, where they can be uptaken by host cells. The transferred cargo may be sufficient to allow MRI detection of these secondarily labeled cells, leading to misinterpretations of the effectiveness of transplanted cells.

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Abbreviations

BMSC:

bone marrow stem cells

FBS:

fetal bovine serum

FISP:

fast steady state precession

FLASH:

fast low-angle shot

HUVEC:

human umbilical vascular endothelial cells

MSC:

mesenchymal stem cells

PMA:

phorbol 12-myristate 13-acetate

SWI:

susceptibility weighted imaging

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ACKNOWLEDGMENTS & DISCLOSURES

This work has been supported by the European project Magnifyco (Contract NMP4- SL-2009-228622). The authors thank Gwennhael Autret and Olivier Clément from the Small Animal Imaging Platform Paris – Descartes at the PARCC-HEGP for MRI imaging, Nicole Boggetto from the Flow Cytometry platform ImagoSeine - Institut Jacques Monod for FACS analysis, Christine Longin and Sophie Chat from Mima2 platform- Inra (Jouy en Josas) for TEM analysis and Pierre Emmanuel Rautou and Chantal Boulanger for fruitful discussion. J. Kolosnjaj-Tabi was supported by the European network ENCITE.

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Authors and Affiliations

  1. Laboratoire Matière et Systèmes Complexes, UMR 7057, CNRS/Université Paris Diderot, Sorbonne Paris Cité, 75205, Paris cedex 13, France

    Amanda K. Andriola Silva, Claire Wilhelm, Jelena Kolosnjaj-Tabi, Nathalie Luciani & Florence Gazeau

  2. INSERM U970, Université Paris Descartes, Sorbonne Paris Cité, Paris Cardiovascular Research Center-PARCC/56 rue Leblanc, 75737, Paris cedex 15, France

    Jelena Kolosnjaj-Tabi

  3. CNRS/Université Paris Diderot, Paris, France

    Florence Gazeau

Authors
  1. Amanda K. Andriola Silva
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  2. Claire Wilhelm
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  3. Jelena Kolosnjaj-Tabi
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  4. Nathalie Luciani
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  5. Florence Gazeau
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Corresponding author

Correspondence to Florence Gazeau.

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Silva, A.K.A., Wilhelm, C., Kolosnjaj-Tabi, J. et al. Cellular Transfer of Magnetic Nanoparticles Via Cell Microvesicles: Impact on Cell Tracking by Magnetic Resonance Imaging. Pharm Res 29, 1392–1403 (2012). https://doi.org/10.1007/s11095-012-0680-1

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  • DOI: https://doi.org/10.1007/s11095-012-0680-1

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