title: Cellular antioxidant levels influence muscle stem cell therapy.
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.
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Drowley
authors.forename: Masaho
authors.initials: M
authors.lastname: Okada
authors.forename: Sarah
authors.initials: S
authors.lastname: Beckman
authors.forename: Joseph
authors.initials: J
authors.lastname: Vella
authors.forename: Bradley
authors.initials: B
authors.lastname: Keller
authors.forename: Kimimasa
authors.initials: K
authors.lastname: Tobita
authors.forename: Johnny
authors.initials: J
authors.lastname: Huard
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008297:Male; D008298:Maleates / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D018482:Muscle, Skeletal / Q000166:cytology*; D009203:Myocardial Infarction / Q000628:therapy; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008298:Maleates; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C014476:diethyl maleate; D000111:Acetylcysteine