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Nerve growth factor improves the muscle regeneration capacity of muscle stem cells in dystrophic muscle.

Lavasani, Mitra and Lu, Aiping and Peng, Hairong and Cummins, James and Huard, Johnny (2006) Nerve growth factor improves the muscle regeneration capacity of muscle stem cells in dystrophic muscle. Hum Gene Ther, 17 (2). 180 - 192. ISSN 1043-0342

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Researchers have attempted to use gene- and cell-based therapies to restore dystrophin and alleviate the muscle weakness that results from Duchenne muscular dystrophy (DMD). Our research group has isolated populations of muscle-derived stem cells (MDSCs) from the postnatal skeletal muscle of mice. In comparison with satellite cells, MDSCs display an improved transplantation capacity in dystrophic mdx muscle that we attribute to their ability to undergo long-term proliferation, self-renewal, and multipotent differentiation, including differentiation toward endothelial and neuronal lineages. Here we tested whether the use of nerve growth factor (NGF) improves the transplantation efficiency of MDSCs. We used two methods of in vitro NGF stimulation: retroviral transduction of MDSCs with a CL-NGF vector and direct stimulation of MDSCs with NGF protein. Neither method of NGF treatment changed the marker profile or proliferation behavior of the MDSCs, but direct stimulation with NGF protein significantly reduced the in vitro differentiation ability of the cells. NGF stimulation also significantly enhanced the engraftment efficiency of MDSCs transplanted within the dystrophic muscle of mdx mice, resulting in the regeneration of numerous dystrophin-positive muscle fibers. These findings highlight the importance of NGF as a modulatory molecule, the study of which will broaden our understanding of its biologic role in the regeneration and repair of skeletal muscle by musclederived cells.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Lavasani, Mitra
Lu, Aiping
Peng, Hairong
Cummins, James
Huard, Johnny
Date: February 2006
Date Type: Publication
Journal or Publication Title: Hum Gene Ther
Volume: 17
Number: 2
Page Range: 180 - 192
DOI or Unique Handle: 10.1089/hum.2006.17.180
Schools and Programs: School of Medicine > Biochemistry and Molecular Genetics
School of Medicine > Orthopaedic Surgery
Swanson School of Engineering > Bioengineering
Refereed: Yes
Uncontrolled Keywords: Animals, Biomarkers, Cell Differentiation, Cell Proliferation, Cell Transplantation, Cells, Cultured, Female, Genetic Therapy, Mice, Mice, Inbred C57BL, Mice, Inbred mdx, Muscle, Skeletal, Muscular Dystrophy, Animal, Nerve Growth Factor, Pluripotent Stem Cells, Regeneration
ISSN: 1043-0342
Related URLs:
Funders: NIAMS NIH HHS (1R01 AR49684-01)
MeSH Headings: Animals; Biological Markers--metabolism; Cell Differentiation; Cell Proliferation; Cell Transplantation; Cells, Cultured; Female; Genetic Therapy--methods; Mice; Mice, Inbred C57BL; Mice, Inbred mdx; Muscle, Skeletal--physiology; Muscle, Skeletal--physiopathology; Muscular Dystrophy, Animal--pathology; Muscular Dystrophy, Animal--therapy; Nerve Growth Factor--analysis; Nerve Growth Factor--genetics; Nerve Growth Factor--pharmacology; Pluripotent Stem Cells--drug effects; Pluripotent Stem Cells--physiology; Regeneration
PubMed ID: 16454652
Date Deposited: 09 Jun 2014 14:58
Last Modified: 20 Dec 2018 00:55


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