Counteracting diabetes-induced adipose tissue derived-stromal cell senescence

Adipose tissue stromal cells (ADSCs) are prone to functional decline and senescence during metabolic disturbances. In diabetes mellitus (DM), the pathogenic microenvironment induces oxidative stress causing ADSCs to senesce. The senescence associated secretory phenotype (SASP) in turn drives disease progression. The pathogenesis of DM is thus both a cause and consequence of senescence. Therapeutically preventing the onset of senescence in ADSCs may play a significant role in preventing disease progression and directly impact the onset of comorbidities. The purpose of this study was to establish an in vitro model that mimic the DM micro-environment to use as a screening tool to assess the therapeutic efficacy of preventative and restorative agents. Exposing ADSCs (cip1, p16^INK4A), apoptosis (p53), inflammation (TNFα, IL6, PTX3, IL10) and adipogenesis (PPARγ, UCP3) was assessed, with AAP pretreatment significantly reducing PTX3 expression. Although this study only investigated the early stages following senescence induction (3 days), subsequent studies could employ this model for longer duration and gain insight into premature senescence and the functional decline of ADSCs within the diabetic context, whilst limiting the use of animals.