Résumé :
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Communication n° 174 INTRODUCTION : Several studies have demonstrated that adult bone marrow-derived cells (BMDC) can participate in skeletal muscle regeneration after bone marrow transplantation (BMT). However, the mechanisms and identities of cell types involved in this process still remain controversial. AIMS :The issue of the study was to evaluate the capacity of BMDC to divide and to differentiate into or fuse to skeletal muscle cells on one hand and to test the therapeutic potentialities of BMDC in a muscular model of Spinal Muscular Atrophy (SMA) on the other hand. METHOD : BMT was performed in a mouse model of SMA, in which deletion of Smn exon 7 has been directed to differentiated myofibers only (Nicole et al., 2003). After irradiation at low dose (6 Gy), 2 month-old mutant mice were either transplanted with unfractionated bone marrow cells (5.10 6) from wild-type (I-BMT WT, n=39) or mutant donor (I-BMT mut, n=11) expressing GFP. Moreover, some mice were irradiated but non transplanted (I-noBMT, n=15) and were considered as the control group. RESULTS : We show that BMTWT was able to improve major phenotypic aspects of irradiated mutant mice including gain of total muscle fibers (+31%), remarkable activation of skeletal muscle regeneration (+56%) and improved motor capacity (+85%). The remarkable attenuation of mutant phenotype contrasts with the low recruitment of BMDC into myofibers (around 2%). Yet, BMT mut which only provides deleted Smn alleles in myofibers abolishes these therapeutic effects. CONCLUSION : Our results strongly suggest that myofibers fused to or differentiated from wild-type but not mutant BMDC deliver paracrine factor(s) which activate(s) skeletal muscle regeneration in vivo leading to therapeutic benefits. Our next goal will be to characterize the paracrine factor(s) involved in the activation of muscle regeneration and to identify the nature of BMDC able to fuse to or differentiate into skeletal muscle fibers.
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