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Title: The combined effects of Young's modulus and low oxygen tension on human induced pluripotent stem cells
Author: Yongsanguanchai, Nuttinee
ISNI:       0000 0004 9352 4574
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2020
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available