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Proc Natl Acad Sci U S A. 2015 Apr 7;112(14):4280-5. doi: 10.1073/pnas.1419799112. Epub 2015 Mar 23.

Sparse feature selection methods identify unexpected global cellular response to strontium-containing materials.

Author information

1
Departments of Materials and Bioengineering and Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, United Kingdom;
2
Departments of Materials and Bioengineering and Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, United Kingdom; Craniofacial Development and Stem Cell Biology, King's College London, London SE1 9RT, United Kingdom;
3
Departments of Materials and Bioengineering and Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, United Kingdom; Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, DK-5230 Odense, Denmark;
4
Departments of Materials and.
5
Cell Biology Group, Biomedical Manufacturing Program, CSIRO Manufacturing Flagship, Clayton 3168, VIC, Australia;
6
Cell Biology Group, Biomedical Manufacturing Program, CSIRO Manufacturing Flagship, Clayton 3168, VIC, Australia; Monash Institute of Pharmaceutical Sciences, Parkville 3052, VIC, Australia; and Latrobe Institute of Molecular Science, Latrobe University, Bundoora 3086, VIC, Australia.
7
Departments of Materials and Bioengineering and Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, United Kingdom; m.stevens@imperial.ac.uk.

Abstract

Despite the increasing sophistication of biomaterials design and functional characterization studies, little is known regarding cells' global response to biomaterials. Here, we combined nontargeted holistic biological and physical science techniques to evaluate how simple strontium ion incorporation within the well-described biomaterial 45S5 bioactive glass (BG) influences the global response of human mesenchymal stem cells. Our objective analyses of whole gene-expression profiles, confirmed by standard molecular biology techniques, revealed that strontium-substituted BG up-regulated the isoprenoid pathway, suggesting an influence on both sterol metabolite synthesis and protein prenylation processes. This up-regulation was accompanied by increases in cellular and membrane cholesterol and lipid raft contents as determined by Raman spectroscopy mapping and total internal reflection fluorescence microscopy analyses and by an increase in cellular content of phosphorylated myosin II light chain. Our unexpected findings of this strong metabolic pathway regulation as a response to biomaterial composition highlight the benefits of discovery-driven nonreductionist approaches to gain a deeper understanding of global cell-material interactions and suggest alternative research routes for evaluating biomaterials to improve their design.

KEYWORDS:

human mesenchymal stem cells; mevalonate pathway; microarray analysis; sparse feature selection analysis; strontium-releasing biomaterials

PMID:
25831522
PMCID:
PMC4394289
DOI:
10.1073/pnas.1419799112
[Indexed for MEDLINE]
Free PMC Article

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