SASP Suppression by hTSCs Secretome
Cellular senescence, a state of irreversible cell cycle arrest, contributes to aging and age-related diseases through the accumulation of senescent cells and their secretion of a pro-inflammatory senescence-associated secretory phenotype (SASP).Recent studies indicated that extracellular vesicles (EVs) as key SASP components mediating intercellular communication. Here, we investigated the effects of human trophoblast stem cell secretome and EVs (hTSC-S, hTSC-EVs) on cellular senescence. Our results show that hTSC-S and hTSC-EVs reduce SASP-associated mRNAs and cytokines, including CXCL1 and GDF15, and suppress NF-?B activation in senescent WI-38 cells. Proteomic analysis revealed an enrichment of ECM-remodeling proteins in hTSC-EVs, suggesting restorative properties. In vivo, hTSC-S decreased GDF15, CXCL1, and markers of DNA damage in aged mice, underscoring its therapeutic potential to modulate SASP and promote healthier aging. Overall design: On Day 1, WI-38 cells were treated with ionizing radiation (IR) and 20% hTSC secretome or control media. On Day 3, the media was refreshed with new media containing 20% hTSC secretome or control. On Day 5, the cells were harvested, and RNA was isolated for RNA-seq analysis.