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Open Access Highly Accessed Research article

Magnetic nanoparticles in primary neural cell cultures are mainly taken up by microglia

Josephine Pinkernelle1*, Pilar Calatayud2, Gerado F Goya23, Hisham Fansa4 and Gerburg Keilhoff1

Author Affiliations

1 Institute of Biochemistry and Cell Biology, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany

2 Instituto de Nanociencia de Aragón (INA), University of Zaragoza, Mariano Esquillor s/n, 50018 Zaragoza, Spain

3 Departamento de Física de la Materia Condensada, Facultad de Ciencias, Universidad de Zaragoza, 50009 Zaragoza, Spain

4 Department of Plastic, Reconstructive and Aesthetic Surgery, Hand Surgery, Klinikum Bielefeld, Teutoburger Str. 50, 33604 Bielefeld, Germany

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BMC Neuroscience 2012, 13:32  doi:10.1186/1471-2202-13-32

Published: 22 March 2012

Abstract

Background

Magnetic nanoparticles (MNPs) offer a large range of applications in life sciences. Applications in neurosciences are one focus of interest. Unfortunately, not all groups have access to nanoparticles or the possibility to develop and produce them for their applications. Hence, they have to focus on commercially available particles. Little is known about the uptake of nanoparticles in primary cells. Previously studies mostly reported cellular uptake in cell lines. Here we present a systematic study on the uptake of magnetic nanoparticles (MNPs) by primary cells of the nervous system.

Results

We assessed the internalization in different cell types with confocal and electron microscopy. The analysis confirmed the uptake of MNPs in the cells, probably with endocytotic mechanisms. Furthermore, we compared the uptake in PC12 cells, a rat pheochromocytoma cell line, which is often used as a neuronal cell model, with primary neuronal cells. It was found that the percentage of PC12 cells loaded with MNPs was significantly higher than for neurons. Uptake studies in primary mixed neuronal/glial cultures revealed predominant uptake of MNPs by microglia and an increase in their number. The number of astroglia and oligodendroglia which incorporated MNPs was lower and stable. Primary mixed Schwann cell/fibroblast cultures showed similar MNP uptake of both cell types, but the Schwann cell number decreased after MNP incubation. Organotypic co-cultures of spinal cord slices and peripheral nerve grafts resembled the results of the dispersed primary cell cultures.

Conclusions

The commercial MNPs used activated microglial phagocytosis in both disperse and organotypic culture systems. It can be assumed that in vivo application would induce immune system reactivity, too. Because of this, their usefulness for in vivo neuroscientific implementations can be questioned. Future studies will need to overcome this issue with the use of cell-specific targeting strategies. Additionally, we found that PC12 cells took up significantly more MNPs than primary neurons. This difference indicates that PC12 cells are not a suitable model for natural neuronal uptake of nanoparticles and qualify previous results in PC12 cells.

Keywords:
Magnetic nanoparticles; Primary neuronal cells; Microglia; Organotypic spinal cord