Document Detail

Nanog reverses the effects of organismal aging on mesenchymal stem cell proliferation and myogenic differentiation potential.
MedLine Citation:
PMID:  22949105     Owner:  NLM     Status:  MEDLINE    
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-β 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.
Juhee Han; Panagiotis Mistriotis; Pedro Lei; Dan Wang; Song Liu; Stelios T Andreadis
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Stem cells (Dayton, Ohio)     Volume:  30     ISSN:  1549-4918     ISO Abbreviation:  Stem Cells     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-27     Completed Date:  2013-09-06     Revised Date:  2013-12-05    
Medline Journal Info:
Nlm Unique ID:  9304532     Medline TA:  Stem Cells     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2746-59     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 AlphaMed Press.
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MeSH Terms
Animals, Newborn
Bone Marrow Cells / cytology,  physiology
Cell Aging / physiology*
Cell Cycle / genetics
Cell Differentiation / physiology
Cell Growth Processes / physiology
Homeodomain Proteins / biosynthesis,  genetics,  physiology*
Mesenchymal Stromal Cells / cytology*,  physiology
Microarray Analysis
Muscle, Smooth, Vascular / cytology,  physiology
Muscles / cytology,  physiology
Signal Transduction
Smad Proteins / metabolism
Transforming Growth Factor beta / metabolism
Young Adult
Grant Support
Reg. No./Substance:
0/Homeodomain Proteins; 0/NANOG protein, human; 0/Smad Proteins; 0/Transforming Growth Factor beta

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