Directional control of neurite outgrowth: emerging technologies for Parkinson's disease using magnetic nanoparticles and magnetic field gradients.

Dhillon, K; Aizel, K; Broomhall, TJ; Secret, E; Goodman, T; Rotherham, M; Telling, N; Siaugue, JM; Ménager, C; Fresnais, J; Coppey, M; El Haj, AJ; Gates, M

doi:10.1098/rsif.2022.0576

Directional control of neurite outgrowth: emerging technologies for Parkinson's disease using magnetic nanoparticles and magnetic field gradients.

Dhillon, K; Aizel, K; Broomhall, TJ; Secret, E; Goodman, T; Rotherham, M; Telling, N; Siaugue, JM; Ménager, C; Fresnais, J; Coppey, M; El Haj, AJ; Gates, M

Authors

K Dhillon

K Aizel

TJ Broomhall

E Secret

T Goodman

M Rotherham

Neil Telling n.d.telling@keele.ac.uk

JM Siaugue

C Ménager

J Fresnais

M Coppey

AJ El Haj

Monte Gates m.a.gates@keele.ac.uk

Abstract

A challenge in current stem cell therapies for Parkinson's disease (PD) is controlling neuronal outgrowth from the substantia nigra towards the targeted area where connectivity is required in the striatum. Here we present progress towards controlling directional neurite extensions through the application of iron-oxide magnetic nanoparticles (MNPs) labelled neuronal cells combined with a magnetic array generating large spatially variant field gradients (greater than 20 T m-1). We investigated the viability of this approach in both two-dimensional and organotypic brain slice models and validated the observed changes in neurite directionality using mathematical models. Results showed that MNP-labelled cells exhibited a shift in directional neurite outgrowth when cultured in a magnetic field gradient, which broadly agreed with mathematical modelling of the magnetic force gradients and predicted MNP force direction. We translated our approach to an ex vivo rat brain slice where we observed directional neurite outgrowth of transplanted MNP-labelled cells from the substantia nigra towards the striatum. The improved directionality highlights the viability of this approach as a remote-control methodology for the control and manipulation of cellular growth for regenerative medicine applications. This study presents a new tool to overcome challenges faced in the development of new therapies for PD.

Journal Article Type	Article
Acceptance Date	Oct 19, 2022
Publication Date	Nov 9, 2022
Journal	Journal of the Royal Society Interface
Print ISSN	1742-5689
Electronic ISSN	1742-5662
Publisher	The Royal Society
Peer Reviewed	Peer Reviewed
Volume	19
Issue	196
DOI	https://doi.org/10.1098/rsif.2022.0576
Keywords	magnetic nanoparticles; regenerative medicine; tissue engineering; neurite outgrowth
Publisher URL	https://royalsocietypublishing.org/doi/10.1098/rsif.2022.0576