Interleukin 6 plays a role in the migration of magnetically levitated mesenchymal stem cells spheroids

Casson, J., O'Kane, S., Smith, C.-A. , Dalby, M. J. and Berry, C. C. (2018) Interleukin 6 plays a role in the migration of magnetically levitated mesenchymal stem cells spheroids. Applied Sciences, 8(3), 412. (doi:10.3390/app8030412)

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Abstract

Mesenchymal stem cells (MSCs) reside quiescently within a specialised ‘niche’ environment in the bone marrow. However, following appropriate signalling cues, MSCs mobilise and migrate out from the niche, typically toward either sites of injury (a regenerative response) or toward primary tumours (an intrinsic homing response, which promotes MSCs as cellular vectors for therapeutic delivery). To date, very little is known about MSC mobilisation. By adopting a 3D MSC niche model, whereby MSC spheroids are cultured within a type I collagen gel, recent studies have highlighted interleukin-6 (IL-6) as a key cytokine involved in MSC migration. Herein, the ability of IL-6 to induce MSC migration was further investigated, and the key matrix metalloproteinases used to effect cell mobilisation were identified. Briefly, the impact of IL-6 on the MSC migration in a two-dimensional model systems was characterised—both visually using an Ibidi chemotaxis plate array (assessing for directional migration) and then via a standard 2D monolayer experiment, where cultured cells were challenged with IL-6 and extracted media tested using an Abcam Human MMP membrane antibody array. The 2D assay displayed a strong migratory response toward IL-6 and analysis of the membrane arrays data showed significant increases of several key MMPs. Both data sets indicated that IL-6 is important in MSC mobilisation and migration. We also investigated the impact of IL-6 induction on MSCs in 3D spheroid culture, serving as a simplistic model of the bone marrow niche, characterised by fluorescently tagged magnetic nanoparticles and identical membrane antibody arrays. An increase in MMP levels secreted by cells treated with 1 ng/mL IL-6 versus control conditions was noted in addition to migration of cells away from the central spheroid mass.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Casson, Jake and Berry, Dr Catherine and Dalby, Professor Matthew and Smith, Mrs Carol-Anne
Authors: Casson, J., O'Kane, S., Smith, C.-A., Dalby, M. J., and Berry, C. C.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Applied Sciences
Publisher:MDPI
ISSN:2076-3417
ISSN (Online):2076-3417
Published Online:11 March 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Applied Sciences 8(3):412
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
619691Nanoparticles and nanotopography: a nano-toolbox to control stem cell self-renewal via microRNAsCatherine BerryBiotechnology and Biological Sciences Research Council (BBSRC)BB/L008661/1RI MOLECULAR CELL & SYSTEMS BIOLOGY