title: Systemic delivery of human bone marrow embryonic-like stem cells improves motor function of severely affected dystrophin/utrophin-deficient mice.
abstract: OBJECTIVE
  Embryonic-like stem cells (ELSCs) express embryonic stem cell-specific marker genes, such as SSEA-4, Oct-4 and Nanog, and can be induced to differentiate into cells of all 3 germ layers. Our preliminary data showed that ELSCs isolated from human bone marrow express multipotent antigen markers and differentiate into multinucleated myotube-like cells more efficiently than do mesenchymal stromal cells (MSCs) isolated from the same source. We investigated the therapeutic effect of ELSCs in dystrophin/utrophin double knock-out (dko) mice, one of the Duchenne muscular dystrophy animal models, by systemically transplanting them through tail-vein injection.
  
  
  METHODS
  ELSCs and MSCs were both isolated from human bone marrow. Two months after equal amounts of ELSCs or MSCs were injected through tail-vein injection, we evaluated skeletal muscle motor function and serum creatine kinase activity and measured dystrophin expression by means of immunostaining, Western blotting and semi-quantitative reverse transcriptase-polymerase chain reaction.
  
  
  RESULTS
  ELSCs positive for Oct-4 and Nanog-3 expressed higher levels of SSEA-4, FZD-9 and CD105 and were induced to differentiate into myotube-like cells more efficiently than did MSCs in vitro. Transplantation of ELSCs through the tail vein improved motor function and decreased serum creatine kinase activity at 2 months after cell transplantation. In addition, dystrophin protein and messenger RNA were upregulated and the skeletal muscle histology was improved in these dko mice transplanted with ELSCs.
  
  
  CONCLUSIONS
  ELSCs could be more efficiently induced to differentiate into myotubes than were MSCs in vitro, and systematically transplanting ELSCs improved muscle motor function and muscle histology in dko mice.
authors.affiliation: Stem Cell Engineering Laboratory of Yunnan Province, Kunming General Hospital of Chengdu Military Command, Kunming, PR China.
authors.forename: Rong-Qing
authors.initials: RQ
authors.lastname: Pang
authors.affiliation: Stem Cell Engineering Laboratory of Yunnan Province, Kunming General Hospital of Chengdu Military Command, Kunming, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.affiliation: Center for Experiment of Yunnan Agricultural University, Kunming, PR China.
authors.forename: Yong-Yun
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Fu
authors.initials: F
authors.lastname: Xiong
authors.affiliation: Stem Cell Engineering Laboratory of Yunnan Province, Kunming General Hospital of Chengdu Military Command, Kunming, PR China.
authors.forename: Guang-Ping
authors.initials: GP
authors.lastname: Ruan
authors.affiliation: Stem Cell Engineering Laboratory of Yunnan Province, Kunming General Hospital of Chengdu Military Command, Kunming, PR China.
authors.forename: Xiang-Qing
authors.initials: XQ
authors.lastname: Zhu
authors.affiliation: Stem Cell Engineering Laboratory of Yunnan Province, Kunming General Hospital of Chengdu Military Command, Kunming, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Stem Cell Engineering Laboratory of Yunnan Province, Kunming General Hospital of Chengdu Military Command, Kunming, PR China.
authors.forename: Jin-Xiang
authors.initials: JX
authors.lastname: Wang
authors.affiliation: Stem Cell Engineering Laboratory of Yunnan Province, Kunming General Hospital of Chengdu Military Command, Kunming, PR China.
authors.forename: Guang-Xu
authors.initials: GX
authors.lastname: Zhu
authors.affiliation: Stem Cell Engineering Laboratory of Yunnan Province, Kunming General Hospital of Chengdu Military Command, Kunming, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Stem Cell Engineering Laboratory of Yunnan Province, Kunming General Hospital of Chengdu Military Command, Kunming, PR China.
authors.forename: Xue-Min
authors.initials: XM
authors.lastname: Cai
authors.affiliation: Stem Cell Engineering Laboratory of Yunnan Province, Kunming General Hospital of Chengdu Military Command, Kunming, PR China. Electronic address: panxinhua@aliyun.com.
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Pan
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, PR China. Electronic address: Zhangcheng100@hotmail.com.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D016189:Dystrophin / Q000172:deficiency*; D053595:Embryonic Stem Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D018345:Mice, Knockout; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation; D049411:Utrophin / Q000172:deficiency*
chemical_list: D000943:Antigens, Differentiation; D016189:Dystrophin; D049411:Utrophin
keywords: Duchenne muscular dystrophy; dko mice; dystrophin; embryonic-like stem cells; mesenchymal stromal cells; transplantation