Nanog Reverses the Effects of Organismal Aging on Mesenchymal Stem Cell Proliferation and Myogenic Differentiation Potential§

Authors

  • Juhee Han,

    1. Department of Chemical and Biological EngineeringUniversity at Buffalo, State University of New York, Amherst, New York, USA
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  • Panagiotis Mistriotis,

    1. Department of Chemical and Biological EngineeringUniversity at Buffalo, State University of New York, Amherst, New York, USA
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  • Pedro Lei,

    1. Department of Chemical and Biological EngineeringUniversity at Buffalo, State University of New York, Amherst, New York, USA
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  • Dan Wang,

    1. Department of Biostatistics, Roswell Park Cancer Institute, Buffalo, New York, USA
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  • Song Liu,

    1. Department of Biostatistics, Roswell Park Cancer Institute, Buffalo, New York, USA
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  • Stelios T. Andreadis

    Corresponding author
    1. Department of Chemical and Biological EngineeringUniversity at Buffalo, State University of New York, Amherst, New York, USA
    2. Department of Biomedical EngineeringUniversity at Buffalo, State University of New York, Amherst, New York, USA
    3. Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, State University of New York, Amherst, New York, USA
    • Bioengineering Laboratory, 908 Furnas Hall, Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Amherst, New York 14260-4200, USA
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    • Telephone: 716-645-1202; Fax: 716-645-3822


  • Author contributions: J.H. and P.M.: collection and/or assembly of data, data analysis and interpretation, and manuscript writing; P.L.: data analysis and interpretation and manuscript writing; D.W. and S.L.: statistical analysis of microarray data; S.T.A.: conception and design, data analysis and interpretation, manuscript writing, and final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS September 4, 2012.

Abstract

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. STEM CELLS 2012;30:2746–2759

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