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Cellular antioxidant levels influence muscle stem cell therapy

Drowley, L and Okada, M and Beckman, S and Vella, J and Keller, B and Tobita, K and Huard, J (2010) Cellular antioxidant levels influence muscle stem cell therapy. Molecular Therapy, 18 (10). 1865 - 1873. ISSN 1525-0016

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Abstract

Although cellular transplantation has been shown to promote improvements in cardiac function following injury, poor cell survival following transplantation continues to limit the efficacy of this therapy. We have previously observed that transplantation of muscle-derived stem cells (MDSCs) improves cardiac function in an acute murine model of myocardial infarction to a greater extent than myoblasts. This improved regenerative capacity of MDSCs is linked to their increased level of antioxidants such as glutathione (GSH) and superoxide dismutase. In the current study, we demonstrated the pivotal role of antioxidant levels on MDSCs survival and cardiac functional recovery by either reducing the antioxidant levels with diethyl maleate or increasing antioxidant levels with N-acetylcysteine (NAC). Both the anti- and pro-oxidant treatments dramatically influenced the survival of the MDSCs in vitro. When NAC-treated MDSCs were transplanted into infarcted myocardium, we observed significantly improved cardiac function, decreased scar tissue formation, and increased numbers of CD31 endothelial cell structures, compared to the injection of untreated and diethyl maleate-treated cells. These results indicate that elevating the levels of antioxidants in MDSCs with NAC can significantly influence their tissue regeneration capacity. © The American Society of Gene & Cell Therapy.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Drowley, L
Okada, M
Beckman, S
Vella, J
Keller, B
Tobita, Kkit3@pitt.eduKIT3
Huard, J
Centers: Other Centers, Institutes, Offices, or Units > Stem Cell Research Center
Date: 1 January 2010
Date Type: Publication
Journal or Publication Title: Molecular Therapy
Volume: 18
Number: 10
Page Range: 1865 - 1873
DOI or Unique Handle: 10.1038/mt.2010.160
Schools and Programs: School of Medicine > Developmental Biology
School of Medicine > Orthopaedic Surgery
School of Medicine > Pathology
School of Medicine > Pediatrics
Refereed: Yes
ISSN: 1525-0016
MeSH Headings: Acetylcysteine--pharmacology; Animals; Antigens, CD31--metabolism; Antioxidants--metabolism; Apoptosis--drug effects; Blotting, Western; Cell Differentiation--drug effects; Cell Proliferation--drug effects; Cell Survival--drug effects; Cell- and Tissue-Based Therapy--methods; Cells, Cultured; Endothelial Cells--cytology; Endothelial Cells--drug effects; Endothelial Cells--metabolism; Enzyme-Linked Immunosorbent Assay; Female; Male; Maleates--pharmacology; Mice; Mice, Inbred C57BL; Mice, SCID; Muscle, Skeletal--cytology; Myocardial Infarction--therapy; Stem Cells--cytology; Stem Cells--drug effects; Stem Cells--metabolism; Vascular Endothelial Growth Factor A--metabolism
Other ID: NLM PMC2951566
PubMed Central ID: PMC2951566
PubMed ID: 20664528
Date Deposited: 04 Apr 2014 16:22
Last Modified: 03 Feb 2019 01:55
URI: http://d-scholarship.pitt.edu/id/eprint/20937

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