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Effect of VEGF on the regenerative capacity of muscle stem cells in dystrophic skeletal muscle

Deasy, BM and Feduska, JM and Payne, TR and Li, Y and Ambrosio, F and Huard, J (2009) Effect of VEGF on the regenerative capacity of muscle stem cells in dystrophic skeletal muscle. Molecular Therapy, 17 (10). 1788 - 1798. ISSN 1525-0016

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Abstract

We have isolated a population of muscle-derived stem cells (MDSCs) that, when compared with myoblasts, display an improved regeneration capacity, exhibit better cell survival, and improve myogenesis and angiogenesis. In addition, we and others have observed that the origin of the MDSCs may reside within the blood vessel walls (endothelial cells and pericytes). Here, we investigated the role of vascular endothelial growth factor (VEGF)-mediated angiogenesis in MDSC transplantation-based skeletal muscle regeneration in mdx mice (an animal model of muscular dystrophy). We studied MDSC and MDSC transduced to overexpress VEGF; no differences were observed in vitro in terms of phenotype or myogenic differentiation. However, after in vivo transplantation, we observe an increase in angiogenesis and endogenous muscle regeneration as well as a reduction in muscle fibrosis in muscles transplanted with VEGF-expressing cells when compared to control cells. In contrast, we observe a significant decrease in vascularization and an increase in fibrosis in the muscles transplanted with MDSCs expressing soluble forms-like tyrosine kinase 1 (sFlt1) (VEGF-specific antagonist) when compared to control MDSCs. Our results indicate that VEGF-expressing cells do not increase the number of dystrophin-positive fibers in the injected mdx muscle, when compared to the control MDSCs. Together the results suggest that the transplantation of VEGF-expressing MDSCs improved skeletal muscle repair through modulation of angiogenesis, regeneration and fibrosis in the injected mdx skeletal muscle.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Deasy, BM
Feduska, JM
Payne, TR
Li, Y
Ambrosio, Ffaa7@pitt.eduFAA7
Huard, J
Centers: Other Centers, Institutes, or Units > Stem Cell Research Center
Date: 15 July 2009
Date Type: Publication
Journal or Publication Title: Molecular Therapy
Volume: 17
Number: 10
Page Range: 1788 - 1798
DOI or Unique Handle: 10.1038/mt.2009.136
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
School of Medicine > Orthopaedic Surgery
School of Medicine > Physical Medicine and Rehabilitation
Swanson School of Engineering > Bioengineering
Refereed: Yes
ISSN: 1525-0016
MeSH Headings: Animals; Cell Differentiation--genetics; Cell Differentiation--physiology; Cell Proliferation; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Immunohistochemistry; Mice; Muscle Development--genetics; Muscle Development--physiology; Muscle, Skeletal--cytology; Muscle, Skeletal--metabolism; Muscle, Skeletal--pathology; Muscular Dystrophy, Animal--therapy; Stem Cell Transplantation--methods; Stem Cells--cytology; Stem Cells--physiology; Transduction, Genetic; Vascular Endothelial Growth Factor A--genetics; Vascular Endothelial Growth Factor A--physiology
Other ID: NLM PMC2835014
PubMed Central ID: PMC2835014
PubMed ID: 19603004
Date Deposited: 09 Apr 2014 15:38
Last Modified: 25 Jan 2019 23:55
URI: http://d-scholarship.pitt.edu/id/eprint/21058

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