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Nanoscale surfaces for the long-term maintenance of mesenchymal stem cell phenotype and multipotency

Nature Materials volume 10, pages 637–644 (2011)Cite this article

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Abstract

There is currently an unmet need for the supply of autologous, patient-specific stem cells for regenerative therapies in the clinic. Mesenchymal stem cell differentiation can be driven by the material/cell interface suggesting a unique strategy to manipulate stem cells in the absence of complex soluble chemistries or cellular reprogramming. However, so far the derivation and identification of surfaces that allow retention of multipotency of this key regenerative cell type have remained elusive. Adult stem cells spontaneously differentiate in culture, resulting in a rapid diminution of the multipotent cell population and their regenerative capacity. Here we identify a nanostructured surface that retains stem-cell phenotype and maintains stem-cell growth over eight weeks. Furthermore, the study implicates a role for small RNAs in repressing key cell signalling and metabolomic pathways, demonstrating the potential of surfaces as non-invasive tools with which to address the stem cell niche.

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Figure 1: Expression of progenitor and osteoblast markers by MSCs cultured on SQ and on controls after four weeks and eight weeks of culture.
Figure 2: MSC multipotency following prolonged culture on the SQ topography.
Figure 3: Pathway analysis of MSCs cultured on SQ, NSQ50 and with OGM compared with planar control.
Figure 4: Metabolic saturation in undifferentiated and differentiating MSCs.
Figure 5: MSC phenotype retention is linked to SNORD up-regulation.
Figure 6: MSC phenotype retention is linked to intraceullular tension and ERK signalling.

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Acknowledgements

Funding for this work is gratefully acknowledged from the following: A Lord Kelvin/Adam Smith Scholarship for R.J.M. from the University of Glasgow, BBSRC follow-on grant BB/FOF/210 and BBSRC project grant BBG0088681 (to M.J.D. and N.G.). Work from ROCO laboratory is funded through BBSRC BB/G006970/1 and we acknowledge the help of the Sir Henry Welcome Functional Genomics Facility with microarray and bioinformatics, especially P. Herzyk. Bone samples from the orthopaedic surgeons at Southampton General Hospital are gratefully acknowledged.

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Authors and Affiliations

  1. 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, Scotland, UK

    Rebecca J. McMurray, P. Monica Tsimbouri, Laura E. McNamara & Matthew J. Dalby

  2. Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT, Scotland, UK

    Nikolaj Gadegaard

  3. Sir Henry Wellcome Functional Genomics Facility, Joseph Black Building, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, Scotland, UK

    Karl V. Burgess

  4. Bone & Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton School of Medicine, Southampton SO16 6YD, UK

    Rahul Tare, Kate Murawski, Emmajayne Kingham & Richard O. C. Oreffo

  5. Department of Anatomy, Stem Cell Unit, College of Medicine, King Saud University, Riyadh 11461, Kingdom of Saudi Arabia

    Richard O. C. Oreffo

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  1. Rebecca J. McMurray
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Contributions

R.J.M. performed most of the practical work and was also involved in experimental design, data analysis and writing of the manuscript. N.G. designed, fabricated and characterized the nanoscale patterns, devised imprinting techniques for the polymers and helped write the manuscript. K.V.B. developed metabolite isolation protocols, ran the mass spectroscopy analysis and helped with bioinformatics. P.M.T. performed experiments on polycarbonate and also performed the integrin and cytoskeletal inhibitor studies. E.K. and R.T. performed most of the qPCR and associated data analysis. L.E.M. analysed the small RNA data and helped write the manuscript. K.M. isolated all the STRO-1 cells, performed passaging experiments and analysed the data. R.O.C.O. lead and designed the Southampton experiments, organized many aspects of the work and helped analyse the data and write the manuscript. M.J.D. designed many of the experiments, analysed the data with R.J.M. and wrote the manuscript.

Corresponding authors

Correspondence to Nikolaj Gadegaard or Matthew J. Dalby.

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The authors declare no competing financial interests.

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McMurray, R., Gadegaard, N., Tsimbouri, P. et al. Nanoscale surfaces for the long-term maintenance of mesenchymal stem cell phenotype and multipotency. Nature Mater 10, 637–644 (2011). https://doi.org/10.1038/nmat3058

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