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Cellular and Molecular Life Sciences CMLS

, Volume 58, Issue 8, pp 1150–1158 | Cite as

Culture in low levels of oxygen enhances in vitro proliferation potential of satellite cells from old skeletal muscles

  • M.V. Chakravarthy
  • E.E. Spangenburg
  • F.W. Booth

Abstract:

The proliferation ability of satellite cells (considered the 'stem cells' of mature myofibers) declines with increasing age when cultured under standard cell culture conditions of 21% oxygen. However, actual oxygen levels in the intact myofiber in vivo are an order of magnitude lower. No studies to date have addressed the issue of whether culturing satellite cells from old muscles under more 'physiologic' conditions would enhance their proliferation and/or differentiation ability. Therefore, we analyzed satellite cells derived from 31-month-old rats in standard cultures with 21% O2 and in lowered (∼3%) O2. Under the lowered O2 conditions, we noted a remarkable increase in the percentage of large-sized colonies, activation of cell cycle progression factors, phosphorylation of Akt, and downregulation of the cell cycle inhibitor p27Kip1. These data suggest that lower O2 levels provide a milieu that stimulates proliferation by allowing continued cell cycle progression, to result ultimately in the enhanced in vitro replicative life span of the old satellite cells. Such a method therefore provides an improved means for the ex vivo generation of progenitor satellite cell populations for potential therapeutic stem cell transplantation.

Key words: Hypoxia; stem cell; cellular senescence; aging; cell cycle; Akt. 

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Copyright information

© Birkhäuser Verlag, 2001

Authors and Affiliations

  • M.V. Chakravarthy
    • 1
  • E.E. Spangenburg
    • 2
  • F.W. Booth
    • 2
  1. 1.University of Texas, Medical School at Houston, Department of Integrative Biology, 6431 Fannin Street, Houston, (Texas 77054, USA)US
  2. 2.University of Missouri-Columbia, Department of Veterinary Biomedical Sciences and Dalton Cardiovascular Institute, 1600 E. Rollins St., E 102 Vet. Med. Bldg., Columbia (Missouri 65211, USA), Fax: +1 573 884 6890, e- mail: boothf@missouri.eduUS

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