Next Generation Biomaterials Discovery for Regenerative Medicine
Human pluripotent stem cells (hPSCs) have the capability to provide a limitless source of physiologically relevant human tissue for drug screening and therapeutic applications. Differentiated cell types can possess an immature phenotype limiting their scope of use, with hPSC-derived cardiomyocytes a...
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| Format: | Thesis (University of Nottingham only) |
| Language: | English English |
| Published: |
2020
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| Online Access: | https://eprints.nottingham.ac.uk/60661/ |
| Summary: | Human pluripotent stem cells (hPSCs) have the capability to provide a limitless source of physiologically relevant human tissue for drug screening and therapeutic applications. Differentiated cell types can possess an immature phenotype limiting their scope of use, with hPSC-derived cardiomyocytes a prominent example. To truly realise the potential of hPSCs, fully defined and xeno-free culture systems must be in place, that are economically viable for industrial scale application. Additionally, the system must be capable of inducing relevant maturation of states of cell types cultured.
In this thesis a readily available and economical polymer library primarily composed of 281 acrylates & acrylamides were screened using polymer microarray technology, totalling 37,103 cell-surface interactions.
Serially passaged hPSCs were examined by RT-qPCR, flow cytometry, immunostaining, trilineage differentiation, integrin blocking, and phosphokinase protein arrays. hPSCs maintained trilineage differentiation capability, with inter-cell line differences discovered for expression of SOX2, SOX1, PAX6, and the phosphorylated state of protein kinases – compared to a Matrigel control.
Polymers that supported ≥7-day hPSC-CM attachment underwent studies into the contraction and electrophysiology properties of hPSC-CMs on primary amine polymeric surfaces compared to the Matrigel. Minor changes to the maturation state were observed, with further examination required for a definitive conclusion. |
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