title: Nanotopography controls cell cycle changes involved with skeletal stem cell self-renewal and multipotency.
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.
authors.affiliation: Centre for Cell Engineering, Institute of Molecular, Cell and Systems Biology, College of Medical Veterinary and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow, G12 8QQ, UK.
authors.forename: Louisa C Y
authors.initials: LC
authors.lastname: Lee
authors.affiliation: Division of Biomedical Engineering, School of Engineering, Rankine Building, University of Glasgow, Glasgow, G12 8LT, UK.
authors.forename: Nikolaj
authors.initials: N
authors.lastname: Gadegaard
authors.affiliation: Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK.
authors.forename: María C
authors.initials: MC
authors.lastname: de Andrés
authors.affiliation: Centre for Cell Engineering, Institute of Molecular, Cell and Systems Biology, College of Medical Veterinary and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow, G12 8QQ, UK.
authors.forename: Lesley-Anne
authors.initials: LA
authors.lastname: Turner
authors.affiliation: Glasgow Polyomics Facility, College of Medical, Veterinary and Life Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Garsube Campus, Bearsden, G61 1QH, UK.
authors.forename: Karl V
authors.initials: KV
authors.lastname: Burgess
authors.affiliation: Institute of Biological Chemistry, Biophysics and Bioengineering, William Perkin Building, Heriot-Watt University, Edinburgh, EH14 4AS, UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Yarwood
authors.affiliation: Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Wells
authors.affiliation: Division of Biomedical Engineering, School of Engineering, Rankine Building, University of Glasgow, Glasgow, G12 8LT, UK.
authors.forename: Manuel
authors.initials: M
authors.lastname: Salmeron-Sanchez
authors.affiliation: Department of Orthopaedics, Queen Elizabeth University Hospital, Glasgow, G51 4TF, UK.
authors.forename: Dominic
authors.initials: D
authors.lastname: Meek
authors.affiliation: Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK.
authors.forename: Richard O C
authors.initials: RO
authors.lastname: Oreffo
authors.affiliation: Centre for Cell Engineering, Institute of Molecular, Cell and Systems Biology, College of Medical Veterinary and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow, G12 8QQ, UK. Electronic address: matthew.dalby@glasgow.ac.uk.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Dalby
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D000066673:Cell Self Renewal / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D053758:Nanoparticles / Q000737:chemistry*; D010006:Osteoblasts / Q000166:cytology* / Q000502:physiology*; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D018797:Cell Cycle Proteins
keywords: Cell cycle; Mesenchymal stem cells; Nanotopography; Skeletal stem cells