title: Fetal muscle-derived cells can repair dystrophic muscles in mdx mice.
abstract: We have previously reported that CD34(+) cells purified from mouse fetal muscles can differentiate into skeletal muscle in vitro and in vivo when injected into muscle tissue of dystrophic mdx mice. In this study, we investigate the ability of such donor cells to restore dystrophin expression, and to improve the functional muscle capacity of the extensor digitorum longus muscle (EDL) of mdx mice. For this purpose green fluorescent-positive fetal GFP(+)/CD34(+) cells or desmin(+)/(-)LacZ/CD34(+) cells were transplanted into irradiated or non-irradiated mdx EDL muscle. Donor fetal muscle-derived cells predominantly fused with existing fibers. Indeed more than 50% of the myofibers of the host EDL contained donor nuclei delivering dystrophin along 80-90% of the length of their sarcolemma. The presence of significant amounts of dystrophin (about 60-70% of that found in a control wild-type mouse muscle) was confirmed by Western blot analyses. Dystrophin expression also outcompeted that of utrophin, as revealed by a spatial shift in the distribution of utrophin. At 1 month post-transplant, the recipient muscle appeared to have greater resistance to fatigue than control mdx EDL muscle during repeated maximal contractions.
authors.affiliation: CNRS UMR 6204, Faculté des Sciences et des Techniques, 44322 Nantes Cedex 3, France.
authors.forename: Gwenola
authors.initials: G
authors.lastname: Auda-Boucher
authors.forename: Thierry
authors.initials: T
authors.lastname: Rouaud
authors.forename: Aude
authors.initials: A
authors.lastname: Lafoux
authors.forename: Dmitri
authors.initials: D
authors.lastname: Levitsky
authors.forename: Corinne
authors.initials: C
authors.lastname: Huchet-Cadiou
authors.forename: Marie
authors.initials: M
authors.lastname: Feron
authors.forename: Laetitia
authors.initials: L
authors.lastname: Guevel
authors.forename: Sophie
authors.initials: S
authors.lastname: Talon
authors.forename: Josiane
authors.initials: J
authors.lastname: Fontaine-Pérus
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Gardahaut
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D002459:Cell Fusion; D003893:Desmin / Q000378:metabolism; D016189:Dystrophin / Q000378:metabolism; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D007763:Lac Operon; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D032342:Muscle Cells / Q000502:physiology / Q000637:transplantation*; D009132:Muscles / Q000196:embryology / Q000528:radiation effects; D009137:Muscular Dystrophy, Animal / Q000628:therapy*
chemical_list: D018952:Antigens, CD34; D003893:Desmin; D016189:Dystrophin; D049452:Green Fluorescent Proteins