The effect of magnetic nanoparticles on neuronal differentiation of induced pluripotent stem cell-derived neural precursors

Abstract

Introduction

Magnetic resonance (MR) imaging is suitable for noninvasive long-term tracking. We labeled human induced pluripotent stem cell-derived neural precursors (iPSC-NPs) with two types of iron-based nanoparticles, silica-coated cobalt zinc ferrite nanoparticles (CZF) and poly-l-lysine-coated iron oxide superparamagnetic nanoparticles (PLL-coated γ-Fe₂O₃) and studied their effect on proliferation and neuronal differentiation.

Materials and methods

We investigated the effect of these two contrast agents on neural precursor cell proliferation and differentiation capability. We further defined the intracellular localization and labeling efficiency and analyzed labeled cells by MR.

Results

Cell proliferation was not affected by PLL-coated γ-Fe₂O₃ but was slowed down in cells labeled with CZF. Labeling efficiency, iron content and relaxation rates measured by MR were lower in cells labeled with CZF when compared to PLL-coated γ-Fe₂O₃. Cytoplasmic localization of both types of nanoparticles was confirmed by transmission electron microscopy. Flow cytometry and immunocytochemical analysis of specific markers expressed during neuronal differentiation did not show any significant differences between unlabeled cells or cells labeled with both magnetic nanoparticles.

Conclusion

Our results show that cells labeled with PLL-coated γ-Fe₂O₃ are suitable for MR detection, did not affect the differentiation potential of iPSC-NPs and are suitable for in vivo cell therapies in experimental models of central nervous system disorders.

Keywords:

• neural precursors
• magnetic resonance imaging
• cell differentiation
• superparamagnetic iron oxide nanoparticles
• ferrites

Acknowledgments

This work was supported by the Ministry of Education, Youth and Sports of CR within the LQ1604 National Sustainability Program II (Project BIOCEV-FAR) and by the project “BIOCEV” (CZ.1.05/1.1.00/02.0109), from the Norwegian Financial Mechanism 2009–2014 and the Ministry of Education, Youth and Sports under Project Contract no MSMT-28477/2014; project 7F14057 and MH CR-DRO (Institute for Clinical and Experimental Medicine IKEM, IN00023001). This paper was presented in part at the 10th Czech Neuroscience Society Meeting, November 18–19, 2015, as a poster presentation with interim findings. The actual paper, however, has never been published. Pavla Jendelová, Daniel Horák and Michal Babič are co-originators of a Eurasian patent no 015718 “Methods of preparation of superparamagnetic nanoparticles based on iron oxides with modified surface and superparamagnetic nanoparticles obtained by such a method” (2011). Pavla Jendelová, Karolina Turnovcová and Pavel Veverka are co-originators of the Czech patent application PV 2015-606 “Nanoparticles for magnetic and fluorescent labeling, their preparation, production and use”.

Disclosure

The authors report no conflicts of interest in this work.