Khalife, Rana;
(2018)
The Effect of the nutritional microenvironment on stem cell differentiation.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
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.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The Effect of the nutritional microenvironment on stem cell differentiation |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2018. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| Keywords: | Stem cells, Germ layer, metabolism |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10064130 |
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