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A Relationship Between Vascular Endothelial Growth Factor, Angiogenesis, and Cardiac Repair After Muscle Stem Cell Transplantation Into Ischemic Hearts

Payne, TR and Oshima, H and Okada, M and Momoi, N and Tobita, K and Keller, BB and Peng, H and Huard, J (2007) A Relationship Between Vascular Endothelial Growth Factor, Angiogenesis, and Cardiac Repair After Muscle Stem Cell Transplantation Into Ischemic Hearts. Journal of the American College of Cardiology, 50 (17). 1677 - 1684. ISSN 0735-1097

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Abstract

Objectives: We investigated whether vascular endothelial growth factor (VEGF) was associated with the angiogenic and therapeutic effects induced after transplantation of skeletal muscle-derived stem cells (MDSCs) into a myocardial infarction (MI). Background: Because very few MDSCs were found to differentiate into new blood vessels when injected into the heart, the mechanism underlying the occurrence of angiogenesis after MDSC transplantation is currently unknown. In the present study, we used a gain- or loss-of-VEGF function approach with skeletal MDSCs engineered to express VEGF or soluble Flt1, a VEGF-specific antagonist, to identify the involvement of VEGF in MDSC transplantation-induced neoangiogenesis. Methods: Vascular endothelial growth factor- and soluble Flt1-engineered MDSCs were injected into an acute MI. Angiogenesis and cardiac function were evaluated by immunohistochemistry and echocardiography. Results: Both control and VEGF-overexpressing MDSCs induced angiogenesis, prevented adverse cardiac remodeling, and improved function compared with saline-injected hearts. However, these therapeutic effects were diminished in hearts transplanted with MDSCs expressing soluble Flt1 despite successful cell engraftment. In vitro experiments demonstrated that MDSCs increased secretion of VEGF in response to hypoxia and cyclic stretch (likely conditions in ischemic hearts), suggesting that transplanted MDSCs release VEGF in vivo. Conclusions: Our findings suggest that VEGF is essential for the induction of angiogenesis and functional improvements observed after MDSC transplantation for infarct repair. © 2007 American College of Cardiology Foundation.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Payne, TR
Oshima, H
Okada, M
Momoi, N
Tobita, Kkit3@pitt.eduKIT3
Keller, BB
Peng, H
Huard, J
Centers: Other Centers, Institutes, or Units > Stem Cell Research Center
Date: 23 October 2007
Date Type: Publication
Journal or Publication Title: Journal of the American College of Cardiology
Volume: 50
Number: 17
Page Range: 1677 - 1684
DOI or Unique Handle: 10.1016/j.jacc.2007.04.100
Schools and Programs: School of Medicine > Biochemistry and Molecular Genetics
School of Medicine > Orthopaedic Surgery
Swanson School of Engineering > Bioengineering
Refereed: Yes
ISSN: 0735-1097
MeSH Headings: Animals; Cells, Cultured; Coronary Circulation; Disease Models, Animal; Male; Mice; Mice, Inbred NOD; Mice, SCID; Muscle, Skeletal--cytology; Myocardial Ischemia--metabolism; Myocardial Ischemia--pathology; Myocardial Ischemia--physiopathology; Myocardial Ischemia--surgery; Myocardium--pathology; Neovascularization, Pathologic--metabolism; Neovascularization, Pathologic--pathology; Neovascularization, Physiologic; Stem Cell Transplantation; Vascular Endothelial Growth Factor A--metabolism; Ventricular Function, Left
PubMed ID: 17950150
Date Deposited: 15 May 2014 20:13
Last Modified: 03 Feb 2019 01:55
URI: http://d-scholarship.pitt.edu/id/eprint/21610

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