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Adipose-derived mesenchymal stem cells from the elderly exhibit decreased migration and differentiation abilities with senescent properties.

Adipose-derived mesenchymal stem cells from the elderly exhibit decreased migration and differentiation abilities with senescent properties.
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Liu M, Lei H, Dong P, Fu X, Yang Z, Yang Y, Ma J, Liu X, Cao Y, Xiao R,


Liu M, Lei H, Dong P, Fu X, Yang Z, Yang Y, Ma J, Liu X, Cao Y, Xiao R, (click to view)

Liu M, Lei H, Dong P, Fu X, Yang Z, Yang Y, Ma J, Liu X, Cao Y, Xiao R,

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Cell transplantation 2017 04 26() doi 10.3727/096368917X695416

Abstract

Adipose-derived stem cells (ADSCs) can be applied extensively in the clinic because they can be easily isolated and cause less donor-site morbidity; however, their application can be complicated by patient-specific factors, such as age and harvest site. In this study, we systematically evaluated the effects of age on the quantity and quality of hADSCs isolated from excised chest subcutaneous adipose tissue and investigated the underlying molecular mechanism. hADSCs were isolated from donors of three different age groups (i.e., child, young adult and elderly). hADSCs are available from individuals across all age groups and maintain mesenchymal stem cell (MSC) characteristics. However, the increased age of the donors was found to have a significant negative effect on the hADSC frequency base on CFU-Fs assay. Moreover, there is a decline in both stromal vascular fraction (SVF) cell yield and the proliferation rate of hADSCs with increasing age, although this relationship is not significant. Aging increases cellular senescence, which is manifested as an increase in SA-β-gal-positive cells, increased mitochondrial-specific ROS production, and the expression of p21 in the elderly. Further, advancing age was found to have a significant negative effect on the adipogenic and osteogenic differentiation potentials of hADSCs, particularly at the early and mid-stages of induction, suggesting a slower response to the inducing factors of hADSCs from elderly donors. Finally, impaired migration ability was also observed in the elderly group and was determined to be associated with decreased expression of chemokine receptors, such as CXCR4 and CXCR7. Taken together, these results suggest that, while hADSCs from different age populations are phenotypically similar, they present major differences at the functional level. When considering potential applications of hADSCs in cell-based therapeutic strategies, the negative influence of age on hADSC differentiation potential and migration abilities should be taken seriously.

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