Nanotopography controls cell cycle changes involved with skeletal stem cell self-renewal and multipotency

Lee, L. et al. (2017) Nanotopography controls cell cycle changes involved with skeletal stem cell self-renewal and multipotency. Biomaterials, 116, pp. 10-20. (doi:10.1016/j.biomaterials.2016.11.032) (PMID:27914982) (PMCID:PMC5226065)

Lee, L. et al. (2017) Nanotopography controls cell cycle changes involved with skeletal stem cell self-renewal and multipotency. Biomaterials, 116, pp. 10-20. (doi:10.1016/j.biomaterials.2016.11.032) (PMID:27914982) (PMCID:PMC5226065)

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Abstract

In culture isolated bone marrow mesenchymal stem cells (more precisely termed skeletal stem cells, SSCs) spontaneously differentiate into fibroblasts, preventing the growth of large numbers of multipotent SSCs for use in regenerative medicine. However, the mechanisms that regulate the expansion of SSCs, while maintaining multipotency and preventing fibroblastic differentiation are poorly understood. Major hurdles to understanding how the maintenance of SSCs is regulated are (a) SSCs isolated from bone marrow are heterogeneous populations with different proliferative characteristics and (b) a lack of tools to investigate SSC number expansion and multipotency. Here, a nanotopographical surface is used as a tool that permits SSC proliferation while maintaining multipotency. It is demonstrated that retention of SSC phenotype in culture requires adjustments to the cell cycle that are linked to changes in the activation of the mitogen activated protein kinases. This demonstrates that biomaterials can offer cross-SSC culture tools and that the biological processes that determine whether SSCs retain multipotency or differentiate into fibroblasts are subtle, in terms of biochemical control, but are profound in terms of determining cell fate.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Yarwood, Dr Stephen and Salmeron-Sanchez, Professor Manuel and Dalby, Professor Matthew and Lee, Miss Louisa and Burgess, Dr Karl and Meek, Professor Dominic and Gadegaard, Professor Nikolaj and Turner, Dr Lesley-Anne
Authors: Lee, L., Gadegaard, N., de Andres, M. C., Turner, L.-A., Burgess, K. V., Yarwood, S. J., Wells, J., Salmeron-Sanchez, M., Meek, D., Oreffo, R. O.C., and Dalby, M. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Biomaterials
Publisher:Elsevier
ISSN:0142-9612
ISSN (Online):1878-5905
Published Online:24 November 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Biomaterials 116:10-20
Publisher Policy:Reproduced under a creative commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
652131Nanoniche - The use of microRNAs and nanotopography to modulate skeletal stem cell fate and functionMatthew DalbyBiotechnology and Biological Sciences Research Council (BBSRC)BB/L023814/1RI MOLECULAR CELL & SYSTEMS BIOLOGY
600931Development of nanopatterned substrates for the delivery of high quality stem cellsNikolaj GadegaardBiotechnology and Biological Sciences Research Council (BBSRC)BB/K011235/1ENG - BIOMEDICAL ENGINEERING