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Beneficial effect of mechanical stimulation on the regenerative potential of muscle-derived stem cells is lost by inhibiting vascular endothelial growth factor

Beckman, SA and Chen, WCW and Tang, Y and Proto, JD and Mlakar, L and Wang, B and Huard, J (2013) Beneficial effect of mechanical stimulation on the regenerative potential of muscle-derived stem cells is lost by inhibiting vascular endothelial growth factor. Arteriosclerosis, Thrombosis, and Vascular Biology, 33 (8). 2004 - 2012. ISSN 1079-5642

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Abstract

OBJECTIVE - : We previously reported that mechanical stimulation increased the effectiveness of muscle-derived stem cells (MDSCs) for tissue repair. The objective of this study was to determine the importance of vascular endothelial growth factor (VEGF) on mechanically stimulated MDSCs in a murine model of muscle regeneration. APPROACH AND RESULTS - : MDSCs were transduced with retroviral vectors encoding the LacZ reporter gene (lacZ-MDSCs), the soluble VEGF receptor Flt1 (sFlt1-MDSCs), or a short hairpin RNA (shRNA) targeting messenger RNA of VEGF (shRNA-VEGF MDSCs). Cells were subjected to 24 hours of mechanical cyclic strain and immediately transplanted into the gastrocnemius muscles of mdx/scid mice. Two weeks after transplantation, angiogenesis, fibrosis, and regeneration were analyzed. There was an increase in angiogenesis in the muscles transplanted with mechanically stimulated lacZ-MDSCs compared with nonstimulated lacZ-MDSCs, sFlt1-MDSCs, and shRNA -VEGF MDSCs. Dystrophin-positive myofiber regeneration was significantly lower in the shRNA-VEGF-MDSC group compared with the lacZ-MDSC and sFlt1-MDSC groups. In vitro proliferation of MDSCs was not decreased by inhibition of VEGF; however, differentiation into myotubes and adhesion to collagen were significantly lower in the shRNA-VEGF-MDSC group compared with the lacZ-MDSC and sFlt1-MDSC groups. CONCLUSIONS - : The beneficial effects of mechanical stimulation on MDSC-mediated muscle repair are lost by inhibiting VEGF. © 2013 American Heart Association, Inc.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Beckman, SA
Chen, WCW
Tang, Yyit3@pitt.eduYIT3
Proto, JD
Mlakar, L
Wang, Bbingwang@pitt.eduBINGWANG
Huard, J
Centers: Other Centers, Institutes, or Units > Stem Cell Research Center
Date: 1 August 2013
Date Type: Publication
Journal or Publication Title: Arteriosclerosis, Thrombosis, and Vascular Biology
Volume: 33
Number: 8
Page Range: 2004 - 2012
DOI or Unique Handle: 10.1161/atvbaha.112.301166
Schools and Programs: School of Medicine > Orthopaedic Surgery
School of Medicine > Pathology
Swanson School of Engineering > Bioengineering
Refereed: Yes
ISSN: 1079-5642
PubMed ID: 23723372
Date Deposited: 31 Mar 2014 15:23
Last Modified: 02 Feb 2019 16:56
URI: http://d-scholarship.pitt.edu/id/eprint/20826

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