期刊
STEM CELLS
卷 30, 期 12, 页码 2746-2759出版社
WILEY
DOI: 10.1002/stem.1223
关键词
Mesenchymal stem cells; Aging; Nanog; Smooth muscle; Contractility; Cardiovascular regeneration
资金
- National Institutes of Health [R01 HL086582]
- New York State Stem Cell Science (NYSTEM Contract) [C024316]
Although the therapeutic potential of mesenchymal stem cells (MSCs) is widely accepted, loss of cell function due to donor aging or culture senescence are major limiting factors hampering their clinical application. Our laboratory recently showed that MSCs originating from older donors suffer from limited proliferative capacity and significantly reduced myogenic differentiation potential. This is a major concern, as the patients most likely to suffer from cardiovascular disease are elderly. Here we tested the hypothesis that a single pluripotency-associated transcription factor, namely Nanog, may reverse the proliferation and differentiation potential of bone marrow-derived MSC (BM-MSC) from adult donors. Microarray analysis showed that adult (a) BM-MSC expressing Nanog clustered close to Nanog-expressing neonatal cells. Nanog markedly upregulated genes involved in cell cycle, DNA replication, and DNA damage repair and enhanced the proliferation rate and clonogenic capacity of aBM-MSC. Notably, Nanog reversed the myogenic differentiation potential and restored the contractile function of aBM-MSC to a similar level as that of neonatal (n) BM-MSC. The effect of Nanog on contractility was mediated-at least in part-through activation of the TGF-beta pathway by diffusible factors secreted in the conditioned medium of Nanog-expressing BM-MSC. Overall, our results suggest that Nanog may be used to overcome the effects of organismal aging on aBM-MSC, thereby increasing the potential of MSC from aged donors for cellular therapy and tissue regeneration. Stem Cells 2012; 30: 2746-2759
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据