• Open Access

Donor Satellite Cell Engraftment Is SignificantlyAugmented When the Host Niche Is Preserved and Endogenous Satellite Cells Are Incapacitated§

Authors

  • Luisa Boldrin,

    Corresponding author
    1. The Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, United Kingdom
    • The Dubowitz Neuromuscular Centre, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, U.K.
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    • Telephone: +44-(0)20-7905-2136; Fax: +44-(0)20-7905-2832

  • Alice Neal,

    1. The Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, United Kingdom
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  • Peter S. Zammit,

    1. Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom
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  • Francesco Muntoni,

    1. The Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, United Kingdom
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  • Jennifer E. Morgan

    Corresponding author
    1. The Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, United Kingdom
    • The Dubowitz Neuromuscular Centre, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, U.K.
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    • Telephone: +44-(0)20-7905-2874; Fax: +44-(0)20-7905-2832


  • Author contributions: L.B.: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing; A.N.: collection, assembly, analysis of data presented in Figure 5; P.Z.: intellectual input into the work, critical reading and final approval of the manuscript; F.M.: intellectual input into the work, critical reading and final approval of the manuscript; J.M.: holder of the grants that fund the project, intellectual input into the work, and manuscript writing.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS June 21, 2012; available online without subscription through the open access option.

Abstract

Stem cell transplantation is already in clinical practice for certain genetic diseases and is a promising therapy for dystrophic muscle. We used the mdx mouse model of Duchenne muscular dystrophy to investigate the effect of the host satellite cell niche on the contribution of donor muscle stem cells (satellite cells) to muscle regeneration. We found that incapacitation of the host satellite cells and preservation of the muscle niche promote donor satellite cell contribution to muscle regeneration and functional reconstitution of the satellite cell compartment. But, if the host niche is not promptly refilled, or is filled by competent host satellite cells, it becomes nonfunctional and donor engraftment is negligible. Application of this regimen to aged host muscles also promotes efficient regeneration from aged donor satellite cells. In contrast, if the niche is destroyed, yet host satellite cells remain proliferation-competent, donor-derived engraftment is trivial. Thus preservation of the satellite cell niche, concomitant with functional impairment of the majority of satellite cells within dystrophic human muscles, may improve the efficiency of stem cell therapy. Stem Cells2012;30:1971–1984

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