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The Combined Effects of Young's Modulus and Low Oxygen Tension on Human Induced Pluripotent Stem Cells

Yongsanguanchai, Nuttinee; (2020) The Combined Effects of Young's Modulus and Low Oxygen Tension on Human Induced Pluripotent Stem Cells. Doctoral thesis (Ph.D), UCL (University College London).

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Nuttinee Yongsanguanchai THESIS - The Combined Effects of Young's Modulus and Low Oxygen Tension on Human Induced Pluripotent Stem Cells.pdf - Accepted version
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Abstract

Human Induced Pluripotent Stem Cells (hiPSCs) have the ability to differentiate into any adult cell type. One of the major challenges in pluripotent stem cell culturing is to improve the yield and efficiency of differentiated cells. Conventional cell culture approaches employ atmospheric oxygen tension (20% O2) and hard tissue culture polystyrene plastic surfaces (Young’s modulus value of 3 x 106 kilopascals). Recent studies have shown that the differentiation of hiPSCs can be influenced and improved by mimicking Young’s moduli or oxygen tension environment experienced by cells in vivo. Based on existing literature, our aim was to expand on the research by mimicking in vivo conditions by combining both factors of Young’s modulus and low oxygen tension during hiPSCs differentiation. The combination of Young’s modulus and low oxygen tension for hiPSCs culture have not been investigated before. In this thesis, the hiPSCs monolayer cultures and aggregates, known as embryoid bodies (EBs), were differentiated for 8 days on polydimethylsiloxane (PDMS) gels with a range of Young’s modulus: 0.2, 2, 16, 64 kilopascals to mimic in vivo conditions. The hiPSCs cells grown on the Young’s modulus: 0.2, 2, 16, 64 kilopascals were also grown both at 2% and 20% oxygen. We discovered that the combination of mechanical environment and low oxygen tension had a significant effect on hiPSCs differentiation. The combination of soft substrates (0.2 kilopascals) and 2% oxygen resulted in an upregulation of endoderm associated genes sry-related HMG box 17 (SOX17), forkhead box A2 (FOXA2) and alpha-fetoprotein (AFP). Whilst both monolayer and EB cultures showed similar responses, the upregulation of these genes was significantly higher in EB cultures, indicating that higer cell-cell contact presented in EB cultures plays a critical role in hiPSCs differentiation. This data indicates that the novel combination of both oxygen and Young’s modulus has the potential to produce endoderm derivatives, such as pancreatic, endothelial and liver cells, which have important roles in drug testing, drug discovery and clinical applications.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The Combined Effects of Young's Modulus and Low Oxygen Tension on Human Induced Pluripotent Stem Cells
Event: UCL (University College London)
Language: English
Additional information: Copyright © The Author 2020. 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.
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 Chemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10092118
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