The CCL7-CCL2-CCR2 Axis Regulates Age-Related Alterations in ADSCs

Abstract Background and ObjectivesAdipose-tissue derived stem cells (ADSCs) autologous transplantation have been a promising strategy for aging-related disorder. But the relationship between ADSCs senescence and organismal aging were still no consistent conclusions. Toward this end, we analyzed the senescence properties of ADSCs from different age donors to furthermore understand the differences of cells between young and senile donors and 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 ResultsWe detected the characteristics, function, gene expression, apoptosis, cell cycle, SA-β-gal staining, and transcription features of ADSCs from 1-month mice and 20-month mice. ADSCs from old donors had some senescence-associated changes with less ability to proliferation than ADSCs from 1-month mice. Differentiation ability, cell surface markers, and SA-β-Gal staining did not differ across donor age, while cells exhibit a more remarkable age-related changes through continuous passages. According to the results of transcriptome analysis, the CCL7-CCL2-CCR2 axis and Hippo signaling pathway would be considered as its possible mechanisms. ConclusionsOur study reveals that ADSCs from old donors have some age-related alterations. The CCL7-CCL2-CCR2 which lies behind this change would be a potential target for gene therapy to reduce harmful effects of ADSCs from old donors. To make autologous transplantation work better, we would recommend that ADSCs should be cryopreserved in youth with minimum number of passages.