Manipulating the Properties of Hydrogels to Promote Ependymal Cell Behaviour for Spinal Cord Repair

Spinal cord injury (SCI) occurs when the spinal cord is physically crushed, impinged, severed, or otherwise damaged; resulting in irreversible disruption to the neuronal pathways responsible for motor and sensory function. The main obstacles to spinal cord repair include neuronal damage, loss of oligodendrocytes (leading to axonal demyelination), and scar formation with glial and fibrotic components. Despite the prevalence of SCI and its costly impact on society, treatment remains limited.
Ependymal cells (ECs) lining the central canal show promise as a pool of endogenous stem cells within the spinal cord. These cells are found to proliferate, differentiate, and migrate in response to injury, however at present, little is known about this neurogenic niche and how the local microenvironment influences cellular behaviour. This project aims to investigate whether endogenous EC behaviour can be altered by manipulating the properties of the surrounding matrix.
Nestin is a type VI intermediate filament protein and a marker of neural stem and progenitor cells in the central nervous system. Characterisation of transgenic mice expressing green fluorescent protein (GFP) under the control of nestin was carried out within this thesis; identifying these cells as ECs and pericytes in the spinal cord. (Nestin) GFP-positive ECs colocalised with a number of stem cell markers including: CD24, Sox2, and foxJ1.
ECs were also shown to express chemokine receptor type 4 (CXCR4), the main receptor to stromal cell-derived factor-1 (SDF-1); both of which are involved in the directed migration of neural cells through chemotaxis. The results of spinal cord slice cultures and intraspinal injections presented in this thesis suggest that EC behaviour can be manipulated using hydrogels and SDF-1α; towards repair of SCI.