Nanotopographical Cues Augment Mesenchymal Differentiation of Human Embryonic Stem Cells

Authors

  • Emmajayne Kingham,

    1. Bone and Joint Research Group, Centre for Human Development, Stem Cells & Regeneration, Human Development and Health, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK
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  • Kate White,

    1. Bone and Joint Research Group, Centre for Human Development, Stem Cells & Regeneration, Human Development and Health, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK
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  • Nikolaj Gadegaard,

    1. Division of Biomedical Engineering, School of Engineering, Rankine Building, University of Glasgow, Glasgow, G12 8LT, UK
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  • Matthew J. Dalby,

    1. Centre for Cell Engineering, Institute of Molecular, Cell & Systems Biology, College of Medical, Veterinary and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow, G12 8QQ, UK
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  • Richard O. C. Oreffo

    Corresponding author
    1. Bone and Joint Research Group, Centre for Human Development, Stem Cells & Regeneration, Human Development and Health, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK
    • Bone and Joint Research Group, Centre for Human Development, Stem Cells & Regeneration, Human Development and Health, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK.
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Abstract

The production of bone-forming osteogenic cells for research purposes or transplantation therapies remains a significant challenge. Using planar polycarbonate substrates lacking in topographical cues and substrates displaying a nanotopographical pattern, mesenchymal differentiation of human embryonic stem cells is directed in the absence of chemical factors and without induction of differentiation by embryoid body formation. Cells incubated on nanotopographical substrates show enhanced expression of mesenchymal or stromal markers and expression of early osteogenic progenitors at levels above those detected in cells on planar substrates in the same basal media. Evidence of epithelial-to-mesenchymal transition during substrate differentiation and DNA methylation changes akin to chemical induction are also observed. These studies provide a suitable approach to overcome regenerative medical challenges and describe a defined, reproducible platform for human embryonic stem cell differentiation.

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