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From stem cell technology to functional restoration after spinal cord injury

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Spinal cord injuries (SCI) have long been regarded as intractable, largely due to the alleged inability of the mammalian CMS to regenerate. However, over the last two decades, technological advances combined with the understanding of the pathophysiology of SCI have progressed to the point where it is now conceivable to develop therapeutic intervention strategies aimed at reconstructing the neuronal circuitry damaged by the lesion. One of the most powerful tools for this objective is based on stem cells, whi ch can be used in three different ways to achieve this goal: 1) to bring permissive molecules and/or trophic agents at the level of the lesion to enhance the regenerative capacity of severed axons; 2) to use as replacement cells, grafted locally to stimula te specific circuits such as the central pattern generator (CPG); 3) to enhance the reparative potential of intrinsic stem cells. Most of the program will concentrate on human adult stem cells generated from bone marrow and adult CNS (including the spinal cord), but we will also consider foetal stem cells and established cell lines. Rodent cells will also be used as a model. This program will be achieved in three steps: Harvesting of adult and/or foetal stem cells (neural and non-neural), to be used directl y or after transformation through genetic engineering. Grafting in the injured cord. Monitoring of the grafted cells with in vivo imaging, and assessing their effects using functional studies. It will require several technical prerequisites including stand ardisation for the harvesting of human stem cells, for the spinal cord lesion models, for the transplantation paradigms and for the functional studies. The final objective of the present project is the translation of experimental studies to clinical practi ce through the elaboration of a series of therapeutic tools to be used in a wide variety of clinical paradigms of SCI.

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FP6-2004-LIFESCIHEALTH-5
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INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE
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