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Stem Cell Res Ther. 2013 Mar 25;4(2):33. doi: 10.1186/scrt183.

Muscle-derived stem/progenitor cell dysfunction in Zmpste24-deficient progeroid mice limits muscle regeneration.

Abstract

INTRODUCTION:

Loss of adult stem cell function during aging contributes to impaired tissue regeneration. Here, we tested the aging-related decline in regeneration potential of adult stem cells residing in the skeletal muscle.

METHODS:

We isolated muscle-derived stem/progenitor cells (MDSPCs) from progeroid Zmpste24-deficient mice (Zmpste24(-/-)) with accelerated aging phenotypes to investigate whether mutation in lamin A has an adverse effect on muscle stem/progenitor cell function.

RESULTS:

Our results indicate that MDSPCs isolated from Zmpste24(-/-) mice show reduced proliferation and myogenic differentiation. In addition, Zmpste24(-/-) MDSPCs showed impaired muscle regeneration, with a limited engraftment potential when transplanted into dystrophic muscle, compared with wild-type (WT) MDSPCs. Exposure of progeroid Zmpste24(-/-) MDSPCs to WT MDSPCs rescued the myogenic differentiation defect in vitro.

CONCLUSIONS:

These results demonstrate that adult stem/progenitor cell dysfunction contributes to impairment of tissue regeneration and suggest that factors secreted by functional cells are indeed important for the therapeutic effect of adult stem cells.

PMID:
23531345
PMCID:
PMC3706820
DOI:
10.1186/scrt183
[Indexed for MEDLINE]
Free PMC Article
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