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MBC in Press, published online ahead of print May 4, 2005
Mol. Biol. Cell 10.1091/mbc.E05-02-0169

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Submitted on February 28, 2005
Accepted on April 22, 2005

Long-Term Self-Renewal of Postnatal Muscle-derived Stem Cells

B. M. Deasy,*{dagger}{ddagger} B. M. Gharaibeh,{dagger} J. B. Pollett,{dagger} M. M. Jones,{dagger} M. A. Lucas,*{dagger} Y. Kanda,{dagger} and J. Huard*{dagger}{ddagger}{sect}

*Department of Bioengineering and {dagger}Growth and Development Laboratory, Children’s Hospital of Pittsburgh, Pittsburgh, PA 15213; Departments of {ddagger}Orthopaedic Surgery and {sect}Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA 15260

Monitoring Editor: Marianne Bronner-Fraser

The ability to undergo self-renewal is a defining characteristic of stem cells. Self-replenishing activity sustains tissue homeostasis and regeneration. In addition, stem cell therapy strategies will require a heightened understanding of the basis of the self-renewal process to enable researchers and clinicians to obtain sufficient numbers of undifferentiated stem cells for cell and gene therapy. Here, we used postnatal muscle-derived stem cells to test the basic biological assumption of unlimited stem cell replication. Muscle-derived stem cells (MDSCs) expanded for 300 population doublings (PDs) showed no indication of replicative senescence. MDSCs preserved their phenotype (ScaI+/CD34+/desminlow) for 200 PDs and were capable of serial transplantation into the skeletal muscle of mdx mice (which model Duchenne muscular dystrophy). MDSCs expanded to this level exhibited high skeletal muscle regeneration comparable to that exhibited by minimally expanded cells. Expansion beyond 200 PDs resulted in lower muscle regeneration, loss of CD34 expression, loss of myogenic activity, and increased growth on soft agar, suggestive of inevitable cell aging attributable to expansion and possible transformation of the MDSCs. Although these results raise questions as to whether cellular transformations derive from cell culturing or provide evidence of cancer stem cells, they establish the remarkable long-term self-renewal and regeneration capacity of postnatal MDSCs.

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




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