Age-related alteration in characteristics, function, and transcription features of ADSCs.

Background And Objectives: Adipose tissue-derived stem cells (ADSCs) autologous transplantation has been a promising strategy for aging-related disorders. However, the relationship between ADSCs senescence and organismal aging has not been clearly established. Therefore, we aimed at evaluating senescence properties of ADSCs from different age donors and to verify the influence of organismal aging on the proliferation and function of ADSCs in vitro, providing the theoretical basis for the clinical application of autologous ADSCs transplantation.

Methods And Results: The ADSCs were obtained from 1-month-old and 20-month-old mice. The cells characteristics, functions, gene expression levels, apoptosis proportion, cell cycle, SA-β-gal staining, and transcription features were evaluated. Compared to ADSCs from 1-month-old mice, ADSCs from 20-month-old mice exhibited some senescence-associated changes, including inhibited abilities to proliferate. Moreover, differentiation abilities, cell surface markers, and cytokines secreting differed between 1M and 20M ADSCs. SA-β-Gal staining did not reveal differences between the two donor groups, while cells exhibited more remarkable age-related changes through continuous passages. Based on transcriptome analysis and further detection, the CCL7-CCL2-CCR2 axis is the most probable mechanism for the differences.

Conclusions: ADSCs from old donors have some age-related alterations. The CCL7-CCL2-CCR2 axis is a potential target for gene therapy to reduce the harmful effects of ADSCs from old donors. To improve on autologous transplantation, we would recommend that ADSCs should be cryopreserved in youth with a minimum number of passages or block CCL7-CCL2-CCR2 to abolish the effects of age-related alterations in ADSCs through the Chemokine signaling pathway.