Résumé :
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Communication n° 169 Therapies are currently investigating the use of the newly identified pluripotent muscle derived stem cells (MDSCs), as a possible cell-mediated therapy, in order to repopulate the dystrophic muscles. The existence of MDSCs, and perhaps the most intriguing and promising application for their use, has evolved from studies investigating myoblast transplantation for the treatment of muscular dystrophies. The clinical possibilities of myoblast transfer therapy (MT) have stimulated a lot of research, although many problems remain to be solved to improve the efficacy of this therapeutic approach. MDSCs are currently investigated as an alternative source to myoblasts to restore dystrophin expression both locally and systemically. In particular, the systemic delivery process, may circumvent one of the major delivery problem facing the use of cellular therapies for treatment of muscular dystrophies, i.e. direct injection of each specific muscle. Despite the demonstration that the intravascular administration of MDSCs is indeed possible, the percentage of dystrophin positive muscle fibers in the mdx mice obtained by this way remained very low. The mechanisms of the transmigration and the signals involved in MDSC recruitment from the circulation still need to be elucidated. An understanding of the mechanisms and identification of factors implicated in homing MDSCs to muscle will be invaluable in our attempts to improve systemic cellular-mediated gene therapy of muscular dystrophies and will have implications for many clinical situations in which MDSC transplantation is appropriate. We described here an approach in which a controlled release technology is used to study in vivo the effect of several candidate substances on MDSC homing process. We have investigated a controlled release system to create a chemo-attracting gradient in the muscle. We have implanted a muscle with biodegradable micro-spheres containing chemo-attracting factors. We have verify whether this increases the extravasation of MDSCs. We consider that any new discovery elucidating the molecular basis involved in MDSC migration from the blood to the muscle may be useful toward the development of systemic cellular-mediated gene therapy of muscle diseases.
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