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Title: Development of novel, robust 3D CNS tissue models for neurobiological studies and drug discovery
Author: O'Rourke, Catriona
ISNI:       0000 0004 5991 910X
Awarding Body: Open University
Current Institution: Open University
Date of Award: 2016
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Recreating the 3D spatial environment of the eNS allows neural cells in vitro to behave more like their counterparts in vivo, providing robust and controllable model systems that mimic key aspects of the cell biology of the nervous system. A simple, consistent and physiologically relevant model system, which uses a multi-well plate format and can potentially be used at a scale suitable for commercial R&D, has been developed. The model uses an engineered neural tissue which is prepared by a process of initial glial cell self-alignment within a tethered 3D collagen hydrogel and subsequent stabilisation of the gel. Stabilisation is achieved using RAFT technology which entails partial removal of interstitial fluid thereby increasing matrix and cell density. To establish viable production technology for the manufacture of eNS tissue models, the parameters that govern glial cell self-alignment were optimised via development of an assay system that requires a small number of cells. A CNS eo-culture system suitable for widespread adoption will require various combinations of cells to suit specific neuroscience research requirements. Both primary neuronal and glial cell types, relevant cell lines and stem cells were incorporated within engineered neural tissues and then assessed using a range of measures including neural cell survival, morphology, differentiation and sensitivity to stabilisation. In a bid to determine the limitations of these 3D eNS model, neuron-glial interactions, markers for myelination, electrophysiological responses and glial cell behaviour in response to injury and insult were also investigated. Initial studies reveal the new model system can be scaled down to facilitate increased throughput, be assembled quickly and reliably using various neural cell sources, and the eo-cultures exhibit characteristic behaviours that mimic in vivo scenarios.
Supervisor: Phillips, James ; Loughlin, Jane ; Cameron, Grant Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available