• Open Access

Age-related changes in mesenchymal stem cells derived from rhesus macaque bone marrow

Authors

  • Ji Min Yu,

    1. Division of Gene Therapy, Tulane National Primate Research Center, Covington, LA 70433, USA
    2. Center for Stem Cell Research and Regenerative Medicine, School of Medicine, Tulane University, New Orleans, LA 70112, USA
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  • Xiying Wu,

    1. Stem Cell Biology Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA
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  • Jeffrey M. Gimble,

    1. Stem Cell Biology Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA
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  • Xiaoyan Guan,

    1. Molecular Virology, Immunology & Medical Genetics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA
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  • Michael A. Freitas,

    1. Molecular Virology, Immunology & Medical Genetics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA
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  • Bruce A. Bunnell

    1. Division of Gene Therapy, Tulane National Primate Research Center, Covington, LA 70433, USA
    2. Center for Stem Cell Research and Regenerative Medicine, School of Medicine, Tulane University, New Orleans, LA 70112, USA
    3. Department of Pharmacology, School of Medicine, Tulane University, New Orleans, LA 70112, USA
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Bruce A. Bunnell, Ph.D. Division of Gene Therapy, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433 USA. Tel.: 985 871 6594; fax: 985 871 6564; e-mail: bbunell@tulane.edu

Summary

The regeneration potential of mesenchymal stem cells (MSCs) diminishes with advanced age and this diminished potential is associated with changes in cellular functions. This study compared MSCs isolated from the bone marrow of rhesus monkeys (rBMSCs) in three age groups: young (< 5 years), middle (8–10 years), and old (> 12 years). The effects of aging on stem cell properties and indicators of stem cell fitness such as proliferation, differentiation, circadian rhythms, stress response proteins, miRNA expression, and global histone modifications in rBMSCs were analyzed. rBMSCs demonstrated decreased capacities for proliferation and differentiation as a function of age. The production of heat shock protein 70 (HSP70) and heat shock factor 1 (HSF1) were also reduced with increasing age. The level of a core circadian protein, Rev-erb α, was significantly increased in rBMSCs from old animals. Furthermore, analysis of miRNA expression profiles revealed an up-regulation of mir-766 and mir-558 and a down-regulation of mir-let-7f, mir-125b, mir-222, mir-199-3p, mir-23a, and mir-221 in old rBMSCs compare to young rBMSCs. However, there were no significant age-related changes in the global histone modification profiles of the four histone core proteins: H2A, H2B, H3, and H4 on rBMSCs. These changes represent novel insights into the aging process and could have implications regarding the potential for autologous stem cells therapy in older patients.

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