Journal
STEM CELLS
Volume 30, Issue 9, Pages 1971-1984Publisher
WILEY
DOI: 10.1002/stem.1158
Keywords
Niche; Satellite cells; Stem cells; Muscle regeneration; Transplantation
Categories
Funding
- Muscular Dystrophy Campaign
- MRC Centre for Neuromuscular Diseases
- Wellcome Trust University award
- Great Ormond Street Hospital Children's Charity
- Medical Research Council
- Wellcome Trust [085137/Z/08/Z, 08241/Z/07/Z]
- OPTISTEM from the European Commission [223098]
- BIODESIGN from the European Commission [262948-2]
- Muscular Dystrophy Campaign [RA3 776]
- Association Francaise contre les Myopathies [13948]
- Wellcome Trust [085137/Z/08/Z] Funding Source: Wellcome Trust
- MRC [G0601943] Funding Source: UKRI
- Medical Research Council [G0601943] Funding Source: researchfish
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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 CELLS 2012;30:1971-1984
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