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

Muscle-derived stem/progenitor cell dysfunction in Zmpste24-deficient progeroid mice limits muscle regeneration.
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DOI:
10.1186/scrt183
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发表时间:
2013-03-25
影响因子:
7.5
通讯作者:
Huard J
Huard J
中科院分区:
医学2区
文献类型:
--
作者:
Song M;Lavasani M;Thompson SD;Lu A;Ahani B;Huard J

文献摘要

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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. 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. 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. 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.