Transcriptomic analysis reveals the anti-cancer effect of gestational mesenchymal stem cell secretome

Vaiasicca, Salvatore, Melone, Gianmarco, James, David W, Quintela, Marcos, Xiao, Jing, Yao, Seydou, Finnell, Richard H, Conlan, Robert S, Francis, Lewis W and Corradetti, Bruna 2024. Transcriptomic analysis reveals the anti-cancer effect of gestational mesenchymal stem cell secretome. Stem Cells Translational Medicine 13 (7) , pp. 693-710. 10.1093/stcltm/szae024

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Abstract

The environment created during embryogenesis contributes to reducing aberrations that drive structural malformations and tumorigenesis. In this study, we investigate the anti-cancer effect of mesenchymal stem cells (MSCs) derived from 2 different gestational tissues, the amniotic fluid (AF) and the chorionic villi (CV), with emphasis on their secretome. Transcriptomic analysis was performed on patient-derived AF- and CV-MSCs collected during prenatal diagnosis and identified both mRNAs and lncRNAs, involved in tissue homeostasis and inhibiting biological processes associated with the etiology of aggressive cancers while regulating immune pathways shown to be important in chronic disorders. Secretome enrichment analysis also identified soluble moieties involved in target cell regulation, tissue homeostasis, and cancer cell inhibition through the highlighted Wnt, TNF, and TGF-β signaling pathways. Transcriptomic data were experimentally confirmed through in vitro assays, by evaluating the anti-cancer effect of the media conditioned by AF- and CV-MSCs and the exosomes derived from them on ovarian cancer cells, revealing inhibitory effects in 2D (by reducing cell viability and inducing apoptosis) and in 3D conditions (by negatively interfering with spheroid formation). These data provide molecular insights into the potential role of gestational tissues-derived MSCs as source of anti-cancer factors, paving the way for the development of therapeutics to create a pro-regenerative environment for tissue restoration following injury, disease, or against degenerative disorders.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Publisher:	Oxford University Press
ISSN:	2157-6564
Date of First Compliant Deposit:	26 July 2024
Date of Acceptance:	12 March 2024
Last Modified:	26 Jul 2024 14:05
URI:	https://orca.cardiff.ac.uk/id/eprint/170898

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