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dc.contributor.authorThorpe, SDen_US
dc.contributor.authorBuckley, CTen_US
dc.contributor.authorSteward, AJen_US
dc.contributor.authorKelly, DJen_US
dc.date.accessioned2018-03-14T16:15:01Z
dc.date.available2012-07-18en_US
dc.date.issued2012-10-11en_US
dc.date.submitted2018-03-12T17:13:25.367Z
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/35783
dc.description.abstractThe aim of this study was to explore how cell-matrix interactions and extrinsic mechanical signals interact to determine stem cell fate in response to transforming growth factor-β3 (TGF-β3). Bone marrow derived mesenchymal stem cells (MSCs) were seeded in agarose and fibrin hydrogels and subjected to dynamic compression in the presence of different concentrations of TGF-β3. Markers of chondrogenic, myogenic and endochondral differentiation were assessed. MSCs embedded within agarose hydrogels adopted a spherical cell morphology, while cells directly adhered to the fibrin matrix and took on a spread morphology. Free-swelling agarose constructs stained positively for chondrogenic markers, with MSCs appearing to progress towards terminal differentiation as indicated by mineral staining. MSC seeded fibrin constructs progressed along an alternative myogenic pathway in long-term free-swelling culture. Dynamic compression suppressed differentiation towards any investigated lineage in both fibrin and agarose hydrogels in the short-term. Given that fibrin clots have been shown to support a chondrogenic phenotype in vivo within mechanically loaded joint defect environments, we next explored the influence of long term (42 days) dynamic compression on MSC differentiation. Mechanical signals generated by this extrinsic loading ultimately governed MSC fate, directing MSCs along a chondrogenic pathway as opposed to the default myogenic phenotype supported within unloaded fibrin clots. In conclusion, this study demonstrates that external cues such as the mechanical environment can override the influence specific substrates, scaffolds or hydrogels have on determining mesenchymal stem cell fate. The temporal data presented in this study highlights the importance of considering how MSCs respond to extrinsic mechanical signals in the long term.en_US
dc.format.extent2483 - 2492en_US
dc.languageengen_US
dc.language.isoenen_US
dc.relation.ispartofJ Biomechen_US
dc.subjectAnimalsen_US
dc.subjectAwards and Prizesen_US
dc.subjectCell Differentiationen_US
dc.subjectCell Survivalen_US
dc.subjectChondrogenesisen_US
dc.subjectFibrinen_US
dc.subjectGene Expression Regulationen_US
dc.subjectHydrogelsen_US
dc.subjectMesenchymal Stem Cellsen_US
dc.subjectMuscle Developmenten_US
dc.subjectSepharoseen_US
dc.subjectStress, Mechanicalen_US
dc.subjectSwineen_US
dc.subjectTransforming Growth Factor beta3en_US
dc.titleEuropean Society of Biomechanics S.M. Perren Award 2012: the external mechanical environment can override the influence of local substrate in determining stem cell fate.en_US
dc.typeArticle
dc.rights.holder© 2012 Elsevier Ltd. All rights reserved.
dc.identifier.doi10.1016/j.jbiomech.2012.07.024en_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/22925995en_US
pubs.issue15en_US
pubs.notesNot knownen_US
pubs.publication-statusPublisheden_US
pubs.volume45en_US
dcterms.dateAccepted2012-07-18en_US


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