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Int. J. Mol. Sci. 2018, 19(8), 2344; https://doi.org/10.3390/ijms19082344

Differential and Interactive Effects of Substrate Topography and Chemistry on Human Mesenchymal Stem Cell Gene Expression

1,†
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2,3,†
,
2,†,‡
,
1,†
,
3
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2
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1,2,4,* and 2,*
1
China National GeneBank-Shenzhen, BGI-Shenzhen, 518083 Shenzhen, China
2
Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, OX3 7DQ Oxford, UK
3
Department of Engineering Science, University of Oxford, OX1 3PJ Oxford, UK
4
Oxford Suzhou Centre for Advanced Research, Suzhou Industrial Park, 215123 Suzhou, China
These authors contributed equally to the paper.
Current address: Department of Applied Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, 695 011 Thiruvananthapuram, India. naresh.kasoju@sctimst.ac.in (N.K.)
*
Authors to whom correspondence should be addressed.
Received: 20 July 2018 / Revised: 5 August 2018 / Accepted: 7 August 2018 / Published: 9 August 2018
(This article belongs to the Special Issue Cell-Biomaterial Interaction)
View Full-Text   |   Download PDF [3105 KB, uploaded 9 August 2018]   |  

Abstract

Variations in substrate chemistry and the micro-structure were shown to have a significant effect on the biology of human mesenchymal stromal cells (hMSCs). This occurs when differences in the surface properties indirectly modulate pathways within numerous signaling networks that control cell fate. To understand how the surface features affect hMSC gene expression, we performed RNA-sequencing analysis of bone marrow-derived hMSCs cultured on tissue culture-treated polystyrene (TCP) and poly(l-lactide) (PLLA) based substrates of differing topography (Fl: flat and Fs: fibrous) and chemistry (Pr: pristine and Am: aminated). Whilst 80% of gene expression remained similar for cells cultured on test substrates, the analysis of differentially expressed genes (DEGs) revealed that surface topography significantly altered gene expression more than surface chemistry. The Fl and Fs topologies introduced opposite directional alternations in gene expression when compared to TCP control. In addition, the effect of chemical treatment interacted with that of topography in a synergistic manner with the Pr samples promoting more DEGs than Am samples in all gene ontology function groups. These findings not only highlight the significance of the culture surface on regulating the overall gene expression profile but also provide novel insights into cell-material interactions that could help further design the next-generation biomaterials to facilitate hMSC applications. At the same time, further studies are required to investigate whether or not the observations noted correlate with subsequent protein expression and functionality of cells. View Full-Text
Keywords: human mesenchymal stromal cells; cell matrix interactions; electrospinning; next generation sequencing; transcriptome human mesenchymal stromal cells; cell matrix interactions; electrospinning; next generation sequencing; transcriptome
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Li, Q.; Zhang, B.; Kasoju, N.; Ma, J.; Yang, A.; Cui, Z.; Wang, H.; Ye, H. Differential and Interactive Effects of Substrate Topography and Chemistry on Human Mesenchymal Stem Cell Gene Expression. Int. J. Mol. Sci. 2018, 19, 2344.

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