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MBC in Press, published online ahead of print November 12, 2008
Mol. Biol. Cell 10.1091/mbc.E08-03-0274

A more recent version of this article appeared on January 1, 2009
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Submitted on March 14, 2008
Revised on October 20, 2008
Accepted on October 31, 2008

Antioxidant Levels Represent a Major Determinant in the Regenerative Capacity of Muscle Stem Cells

Kenneth L. Urish,* Joseph B. Vella,{dagger}{ddagger} Masaho Okada,{ddagger} Bridget M. Deasy,{dagger}{ddagger}{sect} Kimimasa Tobita,|| Bradley B. Keller,|| Baohong Cao,{ddagger} Jon D. Piganelli,|| and Johnny Huard{dagger}{ddagger}{sect}

*Department of Orthopaedic Surgery and Rehabilitation, Penn State Hershey Medical Center, Hershey, PA, 17033; {dagger}Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15260; {ddagger}Stem Cell Research Center, Rangos Research Center, Children’s Hospital of Pittsburgh, Pittsburgh, PA, 15213; {sect}Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, 15260; ||Department of Pediatrics, Children’s Hospital of Pittsburgh, Pittsburgh, PA, 15213; and Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA, 15260

Monitoring Editor: J. Silvio Gutkind

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 as 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.

Address correspondence to: Johnny Huard (jhuard{at}pitt.edu)






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