Résumé :
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Mutations of the survival of motor neuron gene (SMN1) are responsible for Spinal Muscular Atrophy (SMA), a fatal neuromuscular disorder. Mice carrying homozygous deletion of Smn exon 7 directed to skeletal muscle (HSA-Cre, SmnF7/F7 mice), present the main clinical features of human progressive muscular dystrophies. Herein we demonstrate that systemic injection of mouse Amniotic Fluid Stem (AFS) cells increase survival (to 75%, p<0.001) and recovered more than 75% of muscle force with respect to untreated animals. This is probably due to their integration in the muscle stem cell niche. In fact, after cardiotoxin injury performed one month after transplantation, AFS treated mice showed newly regenerating GFP+ muscle fibers (37.86%±9.48 one month after transplantation, 51.75%±1.35 after Ctx injury). Moreover, secondary transplants of satellite cells (SC) derived from treated mice strongly suggest that AFS cells, but not bone marrow cells, integrate in the muscle stem cell compartment and have a long term potential for muscle regeneration comparable to primitive SC from wild type animals (31.47%±2.63 of GFP+ fibers). Similar results were obtained one month after transplantation with injection of expanded AFS cells (21.01%±3.57 of GFP+ fibers). This is the first study demonstrating functional integration of a non-muscle and non-ES derived cells in the SC niche. By the ability of AFS cells to replenish the muscle stem cells niche, AFS cells could represent a promising therapeutic option for muscle-related diseases.
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