Document Detail


Substrate stiffness affects early differentiation events in embryonic stem cells.
MedLine Citation:
PMID:  19768669     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Embryonic stem cells (ESC) are both a potential source of cells for tissue replacement therapies and an accessible tool to model early embryonic development. Chemical factors such as soluble growth factors and insoluble components of the extracellular matrix are known to affect the differentiation of murine ESCs. However, there is also evidence to suggest that undifferentiated cells can both sense the mechanical properties of their environment and differentiate accordingly. By growing ESCs on flexible polydimethylsiloxane substrates with varying stiffness, we tested the hypothesis that substrate stiffness can influence ESC differentiation. While cell attachment was unaffected by the stiffness of the growth substrate, cell spreading and cell growth were all increased as a function of substrate stiffness. Similarly, several genes expressed in the primitive streak during gastrulation and implicated in early mesendoderm differentiation, such as Brachyury, Mixl1 and Eomes, were upregulated in cell cultures on stiffer compared to softer substrates. Finally, we demonstrated that osteogenic differentiation of ESCs was enhanced on stiff substrates compared to soft substrates, illustrating that the mechanical environment can play a role in both early and terminal ESC differentiation. Our results suggest a fundamental role for mechanosensing in mammalian development and illustrate that the mechanical environment should be taken into consideration when engineering implantable scaffolds or when producing therapeutically relevant cell populations in vitro.
Authors:
Nicholas D Evans; Caterina Minelli; Eileen Gentleman; Vanessa LaPointe; Sameer N Patankar; Maria Kallivretaki; Xinyong Chen; Clive J Roberts; Molly M Stevens
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-21
Journal Detail:
Title:  European cells & materials     Volume:  18     ISSN:  1473-2262     ISO Abbreviation:  Eur Cell Mater     Publication Date:  2009  
Date Detail:
Created Date:  2009-09-21     Completed Date:  2010-01-14     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  100973416     Medline TA:  Eur Cell Mater     Country:  Scotland    
Other Details:
Languages:  eng     Pagination:  1-13; discussion 13-4     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Cell Adhesion / drug effects
Cell Differentiation / drug effects*
Cell Movement / drug effects
Cell Proliferation / drug effects
Cells, Cultured
Dimethylpolysiloxanes / chemistry,  pharmacology*
Elasticity
Embryonic Stem Cells / cytology,  drug effects*,  metabolism
Female
Fetal Proteins / genetics
Fibroblast Growth Factor 5 / genetics
Focal Adhesion Kinase 1 / metabolism
GATA6 Transcription Factor / genetics
Gene Expression / drug effects
Hepatocyte Nuclear Factor 3-beta / genetics
Homeodomain Proteins / genetics
Mice
Reverse Transcriptase Polymerase Chain Reaction
SOXB1 Transcription Factors / genetics
T-Box Domain Proteins / genetics
Time Factors
Grant Support
ID/Acronym/Agency:
G0500489//Medical Research Council; //Medical Research Council
Chemical
Reg. No./Substance:
0/Brachyury protein; 0/Dimethylpolysiloxanes; 0/Fetal Proteins; 0/Fgf5 protein, mouse; 0/Foxa2 protein, mouse; 0/GATA6 Transcription Factor; 0/Gata6 protein, mouse; 0/Homeodomain Proteins; 0/Nanog protein, mouse; 0/SOXB1 Transcription Factors; 0/Sox1 protein, mouse; 0/T-Box Domain Proteins; 129653-64-1/Fibroblast Growth Factor 5; 135845-92-0/Hepatocyte Nuclear Factor 3-beta; 63148-62-9/baysilon; EC 2.7.10.2/Focal Adhesion Kinase 1; EC 2.7.10.2/Ptk2 protein, mouse

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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