Substrate stiffness and oxygen as regulators of stem cell differentiation during skeletal tissue regeneration: a mechanobiological model.
Citation:
Burke DP, Kelly DJ, Substrate stiffness and oxygen as regulators of stem cell differentiation during skeletal tissue regeneration: a mechanobiological model., PloS one, 7, 7, 2012, e40737Download Item:
Abstract:
Extrinsic mechanical signals have been implicated as key regulators of mesenchymal stem cell (MSC) differentiation. It has
been possible to test different hypotheses for mechano-regulated MSC differentiation by attempting to simulate
regenerative events such as bone fracture repair, where repeatable spatial and temporal patterns of tissue differentiation
occur. More recently, in vitro studies have identified other environmental cues such as substrate stiffness and oxygen
tension as key regulators of MSC differentiation; however it remains unclear if and how such cues determine stem cell fate in
vivo. As part of this study, a computational model was developed to test the hypothesis that substrate stiffness and oxygen
tension regulate stem cell differentiation during fracture healing. Rather than assuming mechanical signals act directly on
stem cells to determine their differentiation pathway, it is postulated that they act indirectly to regulate angiogenesis and
hence partially determine the local oxygen environment within a regenerating tissue. Chondrogenesis of MSCs was
hypothesized to occur in low oxygen regions, while in well vascularised regions of the regenerating tissue a soft local
substrate was hypothesised to facilitate adipogenesis while a stiff substrate facilitated osteogenesis. Predictions from the
model were compared to both experimental data and to predictions of a well established computational
mechanobiological model where tissue differentiation is assumed to be regulated directly by the local mechanical
environment. The model predicted all the major events of fracture repair, including cartilaginous bridging, endosteal and
periosteal bony bridging and bone remodelling. It therefore provides support for the hypothesis that substrate stiffness and
oxygen play a key role in regulating MSC fate during regenerative events such as fracture healing.
Author's Homepage:
http://people.tcd.ie/kellyd9Description:
PUBLISHED
Author: KELLY, DANIEL JOHN
Type of material:
Journal ArticleSeries/Report no:
PloS one;7;
7;
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Full text availableKeywords:
fracture healingMetadata
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