Natural products and glial cell therapy for repairing the nervous system
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St John, James A
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Davis, Rohan A
Ekberg, Jenny A
Vial, Marie-Laure
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Abstract
The problem: In Australia, over 12,000 people live with a spinal cord injury (SCI) and at least one new case occurs every day. Currently, there is no effective treatment for SCI. Transplantation of olfactory ensheathing cells (OECs; the glial cells of the primary olfactory nervous system) is a promising therapy, in particular autologous transplantation. OECs exhibit unique properties which stimulate neuronal growth and axonal extension, including structural and neurotrophic/guidance support. OECs also function as immune cells and remove (phagocytose) cell debris from the injury site. Furthermore, OECs migrate across the injury site and provide support for regenerating axons. However, functional outcomes in both animal studies and human clinical trials vary greatly, and there are key obstacles in this therapy. These include insufficient cell proliferation rate (both prior to transplantation and after transplantation), cell migration rate and phagocytic activity. If these cell behaviours could be stimulated, the therapeutic potential of OECs would be significantly enhanced. Another important avenue for improvement is the development of novel three-dimensional (3D) cell constructs suitable for both pre-transplantation work (cell culture and drug screening) and for transplantation of OECs directly as a 3D structure into the nervous system injury site. In summary, this work has (1) identified three natural compounds with potential to promote favourable OEC behaviours relevant for neural repair, and (2) led to the development of a novel 3D culture system in which cells rapidly self-assemble without any added ingredients, applicable to a wide range of neural repair avenues. Thus far, the outcomes of this thesis have led to two patent applications, two first-author publications, three first-author manuscripts in submission/preparation, and 1 patent application in preparation, as well as contributing to four papers/manuscripts led by other researchers in the Clem Jones Centre for Neurobiology and Stem Cell Research. The future directions towards enhancing the outcomes of OEC transplantation will be based on the combination of the identified natural products and the developed NLM/NLMNB 3D cell culture methods.
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Thesis (PhD Doctorate)
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Doctor of Philosophy (PhD)
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School of Environment and Sc
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The author owns the copyright in this thesis, unless stated otherwise.
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Subject
spinal cord injury
SCI
Transplantation
olfactory ensheathing cells
OEC
three-dimensional cell constructs
3D cell constructs