title: Antioxidant levels represent a major determinant in the regenerative capacity of muscle stem cells.
abstract: Stem cells are classically defined by their multipotent, long-term proliferation, and self-renewal capabilities. Here, we show that increased antioxidant capacity represents an additional functional characteristic of muscle-derived stem cells (MDSCs). Seeking to understand the superior regenerative capacity of MDSCs compared with myoblasts in cardiac and skeletal muscle transplantation, our group hypothesized that survival of the oxidative and inflammatory stress inherent to transplantation may play an important role. Evidence of increased enzymatic and nonenzymatic antioxidant capacity of MDSCs were observed in terms of higher levels of superoxide dismutase and glutathione, which appears to confer a differentiation and survival advantage. Further when glutathione levels of the MDSCs are lowered to that of myoblasts, the transplantation advantage of MDSCs over myoblasts is lost when transplanted into both skeletal and cardiac muscles. These findings elucidate an important cause for the superior regenerative capacity of MDSCs, and provide functional evidence for the emerging role of antioxidant capacity as a critical property for MDSC survival post-transplantation.
authors.affiliation: Department of Orthopaedics and Rehabilitation, and Department of Surgery, Penn State Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Urish
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Vella
authors.forename: Masaho
authors.initials: M
authors.lastname: Okada
authors.forename: Bridget M
authors.initials: BM
authors.lastname: Deasy
authors.forename: Kimimasa
authors.initials: K
authors.lastname: Tobita
authors.forename: Bradley B
authors.initials: BB
authors.lastname: Keller
authors.forename: Baohong
authors.initials: B
authors.lastname: Cao
authors.forename: Jon D
authors.initials: JD
authors.lastname: Piganelli
authors.forename: Johnny
authors.initials: J
authors.lastname: Huard
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000166:cytology* / Q000502:physiology; D032446:Myoblasts / Q000166:cytology / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016877:Oxidants; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide