Hypoxia mimicking hydrogels to regulate the fate of transplanted stem cells
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Journal ArticleDate:
2019Access:
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O'Brien, K.L. & Kelly, D., Hypoxia mimicking hydrogels to regulate the fate of transplanted stem cells, 2019, Acta Biomaterialia, 88Abstract:
Controlling the phenotype of transplanted stem cells is integral to ensuring their therapeutic
efficacy. Hypoxia is a known regulator of stem cell fate, the effects of which can be mimicked
using hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors such as
dimethyloxalylglycine (DMOG). By releasing DMOG from mesenchymal stem cell (MSC)
laden alginate hydrogels, it is possible to stabilize HIF-1α and enhance its nuclear localization.
This correlated with enhanced chondrogenesis and a reduction in the expression of markers
associated with chondrocyte hypertrophy, as well as increased SMAD 2/3 nuclear localization in
the encapsulated MSCs. In vivo, DMOG delivery significantly reduced mineralisation of the
proteoglycan-rich cartilaginous tissue generated by MSCs within alginate hydrogels loaded with
TGF-β3 and BMP-2. Together these findings point to the potential of hypoxia mimicking
hydrogels to control the fate of stem cells following their implantation into the body
URI:
https://www.sciencedirect.com/science/article/pii/S1742706119301552?via%3Dihubhttp://hdl.handle.net/2262/91352
Sponsor
Grant Number
Science Foundation Ireland
12/US/I2489
Author's Homepage:
http://people.tcd.ie/kellyd9Description:
PUBLISHED
Author: Kelly, Daniel; O'Brien, Katie L.
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Journal ArticleURI:
https://www.sciencedirect.com/science/article/pii/S1742706119301552?via%3Dihubhttp://hdl.handle.net/2262/91352
Series/Report no:
Acta Biomaterialia;88;
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Full text availableKeywords:
Transplanted stem cells, Mesenchymal stem cells, Hydrogel, Stem cell fate, DMOG, Oxygen tension, Hypoxia, Chondrogenesis, HypertrophyDOI:
http://dx.doi.org/10.1016/j.actbio.2019.02.042Metadata
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