Systemic delivery of human bone marrow embryonic-like stem cells improves motor function of severely affected dystrophin/utrophin-deficient mice
| Autor: | Qiang Wang, Xue-Min Cai, Yong-Yun Zhang, Cheng Zhang, Jing Zhao, Xinghua Pan, Xiangqing Zhu, Ruan Guangping, Fu Xiong, Guangxu Zhu, Jie He, Rongqing Pang, Jin-Xiang Wang |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Cancer Research Utrophin Duchenne muscular dystrophy Immunology Bone Marrow Cells Biology Dystrophin Mice medicine Immunology and Allergy Animals Humans Genetics (clinical) Embryonic Stem Cells Stem cell transplantation for articular cartilage repair Mice Knockout Transplantation Myogenesis Mesenchymal stem cell Skeletal muscle Cell Biology medicine.disease Molecular biology Antigens Differentiation Cell biology Muscular Dystrophy Duchenne Disease Models Animal medicine.anatomical_structure Oncology biology.protein Mice Inbred mdx Female Stem cell Stem Cell Transplantation |
| Zdroj: | Cytotherapy. 16(12) |
| ISSN: | 1477-2566 |
| Popis: | Background aims 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. |
| Databáze: | OpenAIRE |
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