Adipose-Derived Mesenchymal Stem Cells from the Elderly Exhibit Decreased Migration and Differentiation Abilities with Senescent Properties

Abstract

Adipose-derived stem cells (ASCs) 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 human adipose-derived mesenchymal stem cells (hASCs) isolated from excised chest subcutaneous adipose tissue and investigated the underlying molecular mechanism. hASCs were isolated from donors of 3 different age-groups (i.e., child, young adult, and elderly). hASCs 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 hASCs frequency base on colony-forming unit fibroblasts assay. Moreover, there is a decline in both stromal vascular fraction (SVF) cell yield and the proliferation rate of hASCs 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 reactive oxygen species (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 hASCs, particularly at the early and mid-stages of induction, suggesting a slower response to the inducing factors of hASCs 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 hASCs from different age populations are phenotypically similar, they present major differences at the functional level. When considering potential applications of hASCs in cell-based therapeutic strategies, the negative influence of age on hASC differentiation potential and migration abilities should be taken seriously.

Base excision repair but not DNA double‐strand break repair is impaired in aged human adipose‐derived stem cells

“…To further test whether age impacts the functions of ADSCs, we examined the osteogenic differentiation potential of ADSCs with Alizarin Red S staining assay. We found that, in agreement with previous reports (Liu et al, 2017), the differentiation potential was impaired in the old groups of ADSCs in comparison to the young cells ( Figure S12 a-b). However, we did not observe any significant correlation between the differentiation potential and BER efficiency or XRCC1 expression ( Figure S12 c-d).…”

Dysregulation of Mesenchymal Stromal Cell Antioxidant Responses in Progressive Multiple Sclerosis

“…PGC1α lacks DNA-binding activity but interacts with and coactivates several transcription factors including Nrf2, which controls constitutive and inducible expression of an array of antioxidant enzymes including SOD, GST, and catalase [35]. Downregulation of PGC1α has been shown to affect the antioxidant response in Friedreich's ataxia [36] and expression of PGC1α has been noted to be lower in adipose tissue-derived MSC from elderly donors [37]. Interestingly, MSC isolated from patients with PSP had fivefold lower levels of expression of PGC1α compared with control MSC [19] and, in an induced pluripotent stem cell model of Parkinson's disease, S-nitrosylation of the transcription factor myocyte enhancer factor 2c (MEF2C) contributes to mitochondrial dysfunction and apoptotic cell death via dysregulation of the PGC1α-MEF2C transcriptional network [38], a Protein expression of SOD1 in response to nitrostative stress in C-MSC and MS-MSC was examined using immunoblotting.…”

P2Y2 and P2Y6 receptor activation elicits intracellular calcium responses in human adipose-derived mesenchymal stromal cells

“…Firstly, only female patients were recruited and no information about ethnicity or lifestyle was collected. The mean age of the recruited donors is 55.5 ± 1.4, and ageing has been shown to increase cellular senescence and AD-MSCs extracted from elderly patients (age 60-73) have been shown to have diminished migration and differentiation capabilities [53]. The molecular mechanisms underlying these changes are not fully understood, so it is not possible to rule out potential changes in the P2 receptor expression and/or functioning as a possible cause.…”