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The Effects of Ageing on the Isolation, Proliferation and Differentiation of Mesenchymal Stem Cells

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The reported effects of ageing on mesenchymal stem cells are variable. A number of studies have shown an age-related decline in the number and proliferation of bone marrow derived mesenchymal stem cells, however a number of other studies found no difference. A number of studies have shown an age-related change in the differentiation potential of mesenchymal stem cells, but this has not been reported in some other studies. Much of the conflicting data in the literature may be due to variations between mesenchymal stem cell donors and in the culture conditions used. It may be that the effect of age on mesenchymal stem cells includes induction of senescence that translates to a reduced cellular output upon culture and transplantation. The molecular pathways involved in the ageing process are complicated and involve the INK4a locus on chromosome 9, p21 that encodes the proteins pI6INK4a. It regulates the p53pathways that promote senescence or apoptosis. The expression of pI6INK4a in particular increases with age and regulates age-dependant senescence, and has been proposed as a biomarker of physiologic as opposed to chronologic age, especially as the expression increases with stress and the accumulation of reactive oxygen species. All of the studies looking at the effects of ageing have concentrated on chronological age as opposed to physiological age, and very few have looked at senescence markers. In this study, we provide a comprehensive review on the effects of ageing in mesenchymal stem cells in humans, mice, rats, rabbit and sheep.

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