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Donor age negatively impacts adipose tissue-derived mesenchymal stem cell expansion and differentiation

作者:Mahmood S. Choudhery, Michael Badowski, Angela Muise, John A. Pierce, David T. Harris · 发表于:Journal of Translational Medicine · 年份:2014 · DOI:10.1186/1479-5876-12-8 · 被引用次数:545 · 研究领域:Mesenchymal stem cell research、Pluripotent Stem Cells Research、Biomedical Ethics and Regulation

BACKGROUND: Human adipose tissue is an ideal autologous source of mesenchymal stem cells (MSCs) for various regenerative medicine and tissue engineering strategies. Aged patients are one of the primary target populations for many promising applications. It has long been known that advanced age is negatively correlated with an organism's reparative and regenerative potential, but little and conflicting information is available about the effects of age on the quality of human adipose tissue derived MSCs (hAT-MSCs). METHODS: To study the influence of age, the expansion and in vitro differentiation potential of hAT-MSCs from young (<30 years), adult (35-50 years) and aged (>60 years) individuals were investigated. MSCs were characterized for expression of the genes p16(INK4a) and p21 along with measurements of population doublings (PD), superoxide dismutase (SOD) activity, cellular senescence and differentiation potential. RESULTS: Aged MSCs displayed senescent features when compared with cells isolated from young donors, concomitant with reduced viability and proliferation. These features were also associated with significantly reduced differentiation potential in aged MSCs compared to young MSCs. CONCLUSIONS: In conclusion, advancing age negatively impacts stem cell function and such age related alterations may be detrimental for successful stem cell therapies.