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:	Creators Email Pitt Username ORCID Beckman, SA Chen, WCW Tang, Y yit3@pitt.edu YIT3 Proto, JD Mlakar, L Wang, B bingwang@pitt.edu BINGWANG Huard, J
Centers:	Other Centers, Institutes, Offices, 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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