The Secretome of Human Trophoblast Stem Cells Attenuates Senescence-Associated Traits.

Kotb Abdelmohsen, Jennifer L Martindale, Martina Rossi, Chang Hoon Shin, Apala Pal, Rachel Munk, Martin Salamini-Montemurri, Mirko Baranzini, Ethan M Arends, Maja Mustapic, Yuta Lee, Jau-Nan Lee, Sicco H Popma, Justin Hu, Nathan Duda, Carlos J Nogueras-Ortiz, Dimitrios Kapogiannis, Chang-Yi Cui, Myriam Gorospe

Laboratory of Genetics and Genomics, National Institute on Aging (NIA) Intramural Research Program (IRP), National Institutes of Health (NIH), Baltimore, Maryland, USA.Laboratory of Genetics and Genomics, National Institute on Aging (NIA) Intramural Research Program (IRP), National Institutes of Health (NIH), Baltimore, Maryland, USA. · pubmed

Paper

Abstract

Senescent cells display indefinite growth arrest and a pro-inflammatory, senescence-associated secretory phenotype (SASP). As the accumulation of senescent cells in tissues with age plays detrimental roles in age-related pathologies, there is much interest in finding therapeutic strategies to eliminate them or suppress the SASP. In this study, we investigated the impact of the secretome and extracellular vesicles (EVs) derived from human trophoblast stem cells (hTSCs) on senescent human fibroblasts. We found that the hTSC conditioned medium (hTSC-CM), and in particular the EVs (hTSC-EVs), significantly reduced the levels of mRNAs encoding SASP factors and the secretion of SASP factors including CXCL1, IL8, and GDF15. Proteomic analysis of hTSC-CM and EVs indicated an enrichment in proteins involved in cell adhesion, tissue repair, and remodeling of the extracellular matrix (ECM). Furthermore, incubation of senescent cells with hTSC-EVs attenuated DNA damage and inflammatory signaling, at least in part by suppressing the function of NF-κB, a major transcriptional regulator of the SASP program. Our findings underscore the value of hTSC-CM and EVs therein in therapeutic approaches directed at senescent cells.

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Research summary

The paper claims that the secretome and extracellular vesicles from human trophoblast stem cells can reduce senescence-associated secretory phenotype factors in senescent human fibroblasts. This research is relevant as it explores a potential therapeutic strategy to mitigate the effects of cellular senescence, which is a key contributor to aging and age-related diseases.

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