title: Activation of Wnt3a signaling promotes myogenic differentiation of mesenchymal stem cells in mdx mice.
abstract: OBJECTIVE
  Duchenne muscular dystrophy (DMD) is an X-linked genetic muscular disorder with no effective treatment at present. Mesenchymal stem cell (MSC) transplantation has been used to treat DMD, but the efficiency is low. Our previous studies show that activation of Wnt3a signaling promotes myogenic differentiation of MSCs in vitro. Here we report an effective MSC transplantation therapy in mdx mice by activation of Wnt3a signaling.
  
  
  METHODS
  MSCs were isolated from mouse bone marrow, and pretreated with Wnt3a-conditioned medium (Wnt3a-CM), then transplanted into mdx mice. The recipient mice were euthanized at 4, 8, 12, 16 weeks after the transplantation, and muscle pathological changes were examined. The expression of dystrophin in muscle was detected using immunofluorescence staining, RT-PCR and Western blotting.
  
  
  RESULTS
  Sixteen weeks later, transplantation of Wnt3a-pretreated MSCs in mdx mice improved the characteristics of dystrophic muscles evidenced by significant reductions in centrally nucleated myofibers, the variability range of cross-sectional area (CSA) and the connective tissue area of myofibers. Furthermore, transplantation of Wnt3a-pretreated MSCs in mdx mice gradually and markedly increased the expression of dystrophin in muscle, and improved the efficiency of myogenic differentiation.
  
  
  CONCLUSIONS
  Transplantation of Wnt3a-pretreated MSCs in mdx mice results in long-term amelioration of the dystrophic phenotype and restores dystrophin expression in muscle. The results suggest that Wnt3a may be a promising candidate for the treatment of DMD.
authors.affiliation: Department of Geriatric Neurology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Yan-Chang
authors.initials: YC
authors.lastname: Shang
authors.affiliation: Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Wang
authors.affiliation: Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Fu
authors.initials: F
authors.lastname: Xiong
authors.affiliation: Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Fu-Ning
authors.initials: FN
authors.lastname: Peng
authors.affiliation: Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Zhen-Shan
authors.initials: ZS
authors.lastname: Liu
authors.affiliation: Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Geng
authors.affiliation: Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D016189:Dystrophin / Q000096:biosynthesis; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology; D051381:Rats; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D060509:Wnt3A Protein / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D017077:Culture Media, Conditioned; D016189:Dystrophin; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse