European Society of Biomechanics S.M. Perren Award 2012: The external mechanical environment can override the influence of local substrate in determining stem cell fate.
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Thorpe SD, Buckley CT, Steward AJ, Kelly DJ, European Society of Biomechanics S.M. Perren Award 2012: The external mechanical environment can override the influence of local substrate in determining stem cell fate., Journal of biomechanics, 45, 15, 2012, 2483-2492Download Item:
Abstract:
The 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-?3
(TGF-?3). 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-?3. 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 toward 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.
Author's Homepage:
http://people.tcd.ie/kellyd9http://people.tcd.ie/thorpes
http://people.tcd.ie/asteward
http://people.tcd.ie/cbuckle
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Journal of biomechanics;45;
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mesenchymal stem cell fateMetadata
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