The disruption of spinal cord motor and sensory pathways following traumatic injury has devastating consequences for damaged patients. Regenerative strategies include the use of cell-based therapies to bridge the lesion. The main objective of this project is to investigate and optimise therapeutic strategies for spinal cord injury (SCI) by combining cell-based therapies with concurrent or sequential application of neuro-protective and/or regenerative pro-factors. We intend to obtain neural-derived embryonic s tem cells to be used for transplantation as prime experiments reported shed hopeful results. However, several questions remain unsolved critical to plan optimised therapies. One of these issues is the mechanism involved regenerative event after cell grafting. By using genetically engineered embryonic stem (ES) cells, we should be able to determine whether regeneration is specifically promoted by cell integration itself into the repaired tissue or by the factors released by them.
An optimal therapeutic strategy for SCI using ES cells will be selected using an in vitro model for neurotrauma based on organotypic spinal cord slice preparations. The establishment of this model is another objective of the project and should facilitate the efficient screening of a broad spectrum of factors in combination with cell graft. It may reduce notably the number of animals destined for this purpose. The most advantageous strategy, derived from this screening will be analysed in vivo on murine models for SCI and functional recovery will be evaluated by a complete battery of electrophysiological and behaviour tests. In summary, the accomplishment of those objectives should shed light into essential neural regenerative processes, may provide innovative systems for high-throughput screenings and should determine optimal therapeutic strategies to repair injured spinal cords.
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