Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies.

By A. Stolzing, E. Jones, D. Mcgonagle, A. Scutt. Mechanisms of Ageing and Development, 2008

1,146 citations recorded by the source corpus.

Human mesenchymal stem cells (hMSC) represent a promising cell-based therapy for a number of degenerative conditions. Understanding the effect of aging on hMSCs is crucial for autologous therapy development in older subject whom degenerative diseases typically afflict. Previous investigations into the effects of aging on hMSC have proved contradictory due to the relative narrow age ranges of subjects assessed and the exclusive reliance of in vitro assays. This study seeks to address this controversy by using a wider range of donor ages and by measuring indices of cellular aging as well as hMSC numbers ex vivo and proliferation rates. CFU-f analysis and flow cytometry analysis using a CD45(low)/D7fib(+ve)/LNGF(+ve) gating strategy were employed. In addition a variety of markers of cellular aging, oxidative damage and senescence measured. A reduction in CFU-f and CD45(low)/D7fib(+ve)/LNGF(+ve) cell numbers were noted in adulthood relative to childhood. Indices of aging including oxidative damage, ROS levels and p21 and p53 all increased suggesting a loss of MSC fitness with age. These data suggest that hMSC numbers obtained by marrow aspiration decline with age. Furthermore, there is an age-related decline in overall BM MSC "fitness" which might lead to problems when using autologous aged MSC for cell-based therapies.

Subfields: Genetics, Hematology, Physiology

View Paper: https://www.semanticscholar.org/paper/d41fe0496922c16fa7eb22af90fbd0d64435e9c6

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Yu Han
Xue-zhou Li
Yanbo Zhang
F. Chang
Jianxun Ding
C. Evans
Hongda Ji
H. Tse

Citations in the corpus

Same or Not the Same? Comparison of Adipose Tissue-Derived Versus Bone Marrow-Derived Mesenchymal Stem and Stromal Cells (2012, neutral): “Additionally, sufﬁcient numbers of BM-MSCs may be more difﬁcult to obtain from a conventional marrow harvest, particularly from the elderly [85], as the number of MSCs decreases with age [137].”
Biologics for tendon repair (2014, background): “Recent investigations focusing on BM-MSC demonstrated apparent agerelated changes such as a reduced proliferation and clonogenicity as well as altered differentiation potential [150,151].”
Mesenchymal Stem Cells for Regenerative Medicine (2019, background): “Moreover, the age of the donors also affects the proliferation and differentiation potential of MSCs, and MSCs from young donors show lower damage and better proliferation [239].”
Mesenchymal stem cells and immunomodulation: current status and future prospects (2016, background): “MSCs derived from young donors show a higher proliferation rate with lower oxidative damage and cell senescence.(117)”