Nanotopography controls cell cycle changes involved with skeletal stem cell self-renewal and multipotency
Nanotopography controls cell cycle changes involved with skeletal stem cell self-renewal and multipotency
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
10-20
Lee, Louisa C.Y.
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Gadegaard, Nikolaj
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de Andrés, María C.
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Turner, Lesley-Anne
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Burgess, Karl V.
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Yarwood, Stephen J.
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Wells, Julia
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Salmeron-Sanchez, Manuel
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Meek, Dominic
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Oreffo, Richard O.C
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Dalby, Matthew J.
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February 2017
Lee, Louisa C.Y.
48fda0e5-2988-4b93-b299-d02925a31946
Gadegaard, Nikolaj
bf72c3d1-e6a7-48b4-a968-c496b655bd98
de Andrés, María C.
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Turner, Lesley-Anne
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Burgess, Karl V.
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Yarwood, Stephen J.
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Wells, Julia
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Salmeron-Sanchez, Manuel
74e2e726-2545-433a-8a7f-4a93a0cbae21
Meek, Dominic
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Oreffo, Richard O.C
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Dalby, Matthew J.
25dcae6a-8289-4169-abb7-c45fff0bafdc
Lee, Louisa C.Y., Gadegaard, Nikolaj, de Andrés, María C., Turner, Lesley-Anne, Burgess, Karl V., Yarwood, Stephen J., Wells, Julia, Salmeron-Sanchez, Manuel, Meek, Dominic, Oreffo, Richard O.C and Dalby, Matthew J.
(2017)
Nanotopography controls cell cycle changes involved with skeletal stem cell self-renewal and multipotency.
Biomaterials, 116, .
(doi:10.1016/j.biomaterials.2016.11.032).
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
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Accepted/In Press date: 23 November 2016
e-pub ahead of print date: 24 November 2016
Published date: February 2017
Organisations:
Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences
Identifiers
Local EPrints ID: 404366
URI: http://eprints.soton.ac.uk/id/eprint/404366
ISSN: 0142-9612
PURE UUID: 51e1ff3c-5927-4275-bb30-45e52c2e9506
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Date deposited: 06 Jan 2017 11:49
Last modified: 16 Mar 2024 04:07
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Contributors
Author:
Louisa C.Y. Lee
Author:
Nikolaj Gadegaard
Author:
María C. de Andrés
Author:
Lesley-Anne Turner
Author:
Karl V. Burgess
Author:
Stephen J. Yarwood
Author:
Julia Wells
Author:
Manuel Salmeron-Sanchez
Author:
Dominic Meek
Author:
Matthew J. Dalby
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