Analysis of the Impact Trophoblast-derived Extracellular Vesicles in Cell Senescence

National Institute On Aging

Investigators

Abstract

Despite the advancements in understanding MSC-derived EVs in aging and senescence, human trophoblast stem cell-derived EVs (hTSC-EVs) have not been studied in these contexts. TSCs are characterized by their scalability, cost-effectiveness as a platform for developing therapies, and their high rate of population doublings with a relatively short doubling time. Importantly, TSCs exhibit immune privilege given their presence in embryonic tissues, achieved through the expression of HLA-G, which is maintained even after differentiation, and increases their potential use in various therapeutic applications. Recent studies on trophoblast-derived conditioned medium (TB-CM) have shown its ability to stimulate osteogenesis through the activation of signaling pathways including the MAPK and BMP2 signaling cascades. This indicates that trophoblast-derived secretomes could be valuable in clinical applications for organ regeneration. Since EVs are major part of the secretome, we aim to isolate and characterize hTSC-EVs from CM (AIM 1), evaluate their impact on cellular senescence (AIM 2), and evaluate the in vivo impact of hTSC-EVs on mouse aging (AIM 3).