Walder, Sally; (2003) Neural progenitors in human and newt spinal cord: An in-vivo and in-vitro study. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

Spinal cord injury in mammals is usually irreversible whereas urodele amphibians are able to regenerate damaged spinal cord. I have carried out a comparative study of human embryonic spinal cord and spinal cord from normal and regenerating newts in vivo and in vitro in order to try and elucidate the mechanisms underlying the regenerative capacity of newts and the reasons behind the mammalian system's inability to effect this type of functional repair. Immunohistochemical analysis of ependymal and progenitor cell markers in human embryonic and regenerating newt spinal cords revealed interesting parallels in the expression of these proteins within the two systems, particularly the intermediate filament protein nestin, a progenitor cell marker. Further analyses of newt and human spinal cord, focusing particularly on the latter, were undertaken in vitro, once the optimal conditions for growth of explants and dissociated spinal cords from the two species had been established. Cell types were characterised by immunocytochemistry. The results obtained from the in vitro studies indicated that in both species the survival and proliferation of progenitor cells was favoured under conditions where cultures were maintained in serum-free media, whereas differentiated cell growth was poor in the absence of serum. Indeed, subsequent studies in which I grew human spinal cord progenitor cells as neurospheres, indicated that serum-free medium was necessary to prevent the spheres from undergoing extensive differentiation, and that when exposed to serum these spinal-cord-derived spheres could give rise to both neurones and glial cells. Finally, in order to study the early response to injury in the human embryonic spinal cord, I have established a novel in vitro injury model system in which whole segments of spinal cord can be cultured in collagen gel and injured by hemisection. TUNEL analysis indicates the occurrence of injury-localised apoptosis in the cultured cords, mirroring one of the pathological injury responses seen in the spinal cord of adult mammals in vivo. This in vitro system may be useful as a model for future studies of the response of human spinal cord to injury.

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