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Title: The effect of the nutritional microenvironment on stem cell differentiation
Author: Khalife, Rana
ISNI:       0000 0004 7659 9371
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2018
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Pluripotent stem cells (PSCs) are considered to be one of the most promising sources of cells for a wide range of regenerative cell therapies. One major challenge remains the efficient induction of differentiation. Initial studies on the effect of low oxygen on pluripotency maintenance was per-formed on different cell lines. Culturing stem cells at low oxygen helped in the maintenance of pluripotency in most of the cell lines except feeder-free human in-duced pluripotent stem cells (hiPSCs; BJ). These findings show for the first time that the maintenance of pluripotency at low oxygen tensions is cell line dependent re-sponse and may be due to one or more of the many associated micro-environmental cues. Moreover, we hypothesised that high glucose, pyruvate and oxygen concen-trations of typical growth media could be inhibiting the differentiation of certain line-ages because they are so different from the environment experienced by developing embryos in-vivo. A design of experiments (DoE) was used to investigate the inter-play between each three during the spontaneous differentiation of hiPSCs (cord blood). Based on this initial screen we discovered that low oxygen and glucose en-hanced the mesodermal and ectodermal lineages. While glucose deprivation was a potent inducer of endodermal lineage formation as 72.73% of the hiPSCs (cord blood) were apoptotic. It was found that apoptosis triggered by staurosporine com-mitted the cells into endodermal lineage. Western blotting analysis revealed that the pathway by which glucose removal enhanced endodermal lineage could be time de-pendent. Thus, the manipulation of energy levels triggered apoptosis which in return enriched the endodermal germ layer selection. The manipulation of the nutritional environment especially glucose deprivation, is a potential approach for the en-hancement of endodermal precursors.
Supervisor: Veraitch, F. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available