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Zmpste24基因缺陷早衰小鼠中肌肉来源的干/祖细胞功能障碍限制了肌肉再生。

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

作者信息

Song Minjung, Lavasani Mitra, Thompson Seth D, Lu Aiping, Ahani Bahar, Huard Johnny

出版信息

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

DOI:10.1186/scrt183
PMID:23531345
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3706820/
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.

摘要

引言

衰老过程中成年干细胞功能的丧失会导致组织再生受损。在此，我们测试了骨骼肌中成年干细胞再生潜能与衰老相关的下降情况。

方法

我们从具有加速衰老表型的早衰型Zmpste24基因缺陷小鼠（Zmpste24(-/-)）中分离出肌肉来源的干细胞/祖细胞（MDSPCs），以研究核纤层蛋白A的突变是否对肌肉干细胞/祖细胞功能有不利影响。

结果

我们的结果表明，从Zmpste24(-/-)小鼠中分离出的MDSPCs增殖和肌源性分化能力降低。此外，与野生型（WT）MDSPCs相比，Zmpste24(-/-) MDSPCs的肌肉再生受损，移植到营养不良肌肉中时植入潜能有限。将早衰型Zmpste24(-/-) MDSPCs与WT MDSPCs共同培养可在体外挽救其肌源性分化缺陷。

结论

这些结果表明成年干细胞/祖细胞功能障碍会导致组织再生受损，并提示功能细胞分泌的因子确实对成年干细胞的治疗效果很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8a7/3706820/004c3abc9cc6/scrt183-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8a7/3706820/a1f92257d1cc/scrt183-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8a7/3706820/20abff9f3c96/scrt183-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8a7/3706820/40b6eb5c4ee5/scrt183-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8a7/3706820/004c3abc9cc6/scrt183-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8a7/3706820/a1f92257d1cc/scrt183-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8a7/3706820/20abff9f3c96/scrt183-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8a7/3706820/40b6eb5c4ee5/scrt183-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8a7/3706820/004c3abc9cc6/scrt183-4.jpg

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