Next Article in Journal
Enhanced Osteogenic Differentiation of Human Fetal Cartilage Rudiment Cells on Graphene Oxide-PLGA Hybrid Microparticles
Previous Article in Journal
The Role of In Vitro Immune Response Assessment for Biomaterials
Open AccessArticle

Novel Tools towards Magnetic Guidance of Neurite Growth: (I) Guidance of Magnetic Nanoparticles into Neurite Extensions of Induced Human Neurons and In Vitro Functionalization with RAS Regulating Proteins

1
Department of Biochemistry II–Molecular Neurobiochemistry, Faculty of Chemistry and Biochemistry, Ruhr-Universität Bochum, 44801 Bochum, Germany
2
Physico-chimie des Électrolytes et Nanosystèmes Interfaciaux, PHENIX, Sorbonne Université, CNRS, F-75005 Paris, France
3
Department of Biochemistry II–Electrobiochemistry of Neural Cells, Faculty of Chemistry and Biochemistry, Ruhr-Universität Bochum, 44801 Bochum, Germany
4
Department of Anatomy and Molecular Embryology, Faculty of Medicine, Ruhr-Universität Bochum, 44801 Bochum, Germany
5
Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany
*
Author to whom correspondence should be addressed.
J. Funct. Biomater. 2019, 10(3), 32; https://doi.org/10.3390/jfb10030032
Received: 24 May 2019 / Revised: 8 July 2019 / Accepted: 11 July 2019 / Published: 16 July 2019
Parkinson’s disease (PD) is a neurodegenerative disease associated with loss or dysfunction of dopaminergic neurons located in the substantia nigra (SN), and there is no cure available. An emerging new approach for treatment is to transplant human induced dopaminergic neurons directly into the denervated striatal brain target region. Unfortunately, neurons grafted into the substantia nigra are unable to grow axons into the striatum and thus do not allow recovery of the original connectivity. Towards overcoming this general limitation in guided neuronal regeneration, we develop here magnetic nanoparticles functionalized with proteins involved in the regulation of axonal growth. We show covalent binding of constitutive active human rat sarcoma (RAS) proteins or RAS guanine nucleotide exchange factor catalytic domain of son of sevenless (SOS) by fluorescence correlation spectroscopy and multiangle light scattering as well as the characterization of exchange factor activity. Human dopaminergic neurons were differentiated from neural precursor cells and characterized by electrophysiological and immune histochemical methods. Furthermore, we demonstrate magnetic translocation of cytoplasmic γ-Fe2O3@SiO2 core-shell nanoparticles into the neurite extensions of induced human neurons. Altogether, we developed tools towards remote control of directed neurite growth in human dopaminergic neurons. These results may have relevance for future therapeutic approaches of cell replacement therapy in Parkinson’s disease. View Full-Text
Keywords: RAS GTPase; GTP exchange factor; SOS; magnetic nanoparticle; Parkinson’s disease; regeneration; dopaminergic neuron; fluorescence correlation spectroscopy; multiangle light scattering; magnetic nanoparticles RAS GTPase; GTP exchange factor; SOS; magnetic nanoparticle; Parkinson’s disease; regeneration; dopaminergic neuron; fluorescence correlation spectroscopy; multiangle light scattering; magnetic nanoparticles
Show Figures

Figure 1

MDPI and ACS Style

Schöneborn, H.; Raudzus, F.; Secret, E.; Otten, N.; Michel, A.; Fresnais, J.; Ménager, C.; Siaugue, J.-M.; Zaehres, H.; Dietzel, I.D.; Heumann, R. Novel Tools towards Magnetic Guidance of Neurite Growth: (I) Guidance of Magnetic Nanoparticles into Neurite Extensions of Induced Human Neurons and In Vitro Functionalization with RAS Regulating Proteins. J. Funct. Biomater. 2019, 10, 32.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map

1
Back to TopTop