Abstract
Adipose-derived mesenchymal stem cells (AdMSCs) are capable of self-renewal and multipotential differentiation and are expected to be utilized in a broad swathe of therapeutic applications. There have been very few studies on the effects of cellular senescence on the differentiation ability of AdMSCs. The purpose of this study is to determine how chronological and biological aging affects the potential of human-derived AdMSCs. We assessed the cellular senescence of AdMSCs isolated from donors in their 20s, 60s, and 80s by conventional assays such as cell proliferation and senescence-associated β-galactosidase (SA- β-Gal) assays. We also performed differentiation assays using early- and late-passage AdMSCs from all age groups. There were no differences in cell proliferation potential among all groups, furthermore, all evaluations for cellular senescence except SA- β-Gal activity and NAMPT gene expression, were comparable among all age groups at the early passage. At the late passage, AdMSCs from all age groups underwent cellular senescence, although those from the elder groups seemed more prominent than those of the 20s. Differentiation potentials tested in this study tended to decline over passages regardless of age, intriguingly, potentials for chondrocyte and osteoblast differentiations were retained across all ages at the early passage. Our results demonstrate that cellular senescence has a more pronounced effect than chronological age on AdMSC functions. Furthermore, this suggests that although early-passage AdMSCs of elderly donors may have already started altering cellular context toward cellular senescence, they are useful in developing some regenerative therapies for elderly patients with autologous cells.
