Molecular insights in the anti-cancer potential of mesenchymal stem cells derived from the amniotic fluid and chorionic villi
The environment created during embryogenesis contributes to reducing aberrations that drive structural malformations and tumorigenesis. In this study, we investigate the anti-cancer potential of mesenchymal stem cells (MSCs) derived from two different gestational tissues, the amniotic fluid (AF) and the chorionic villi (CV), with particular emphasis on the role of the paracrine signals they release. Methods: Next generation sequencing was performed on patient-derived AF- and CV-MSCs to obtain molecular insights into the molecular mechanisms driving their anti-cancer features. Secretome enrichment analysis allowed the identification of soluble moieties involved in target cell regulation, tissue homeostasis and cancer cell inhibition. Data were experimentally confirmed through in vitro assays, by evaluating the cytotoxic effect of the media conditioned (CM) by AF- and CV-MSCs and their derived exosomes (EXO) on two human ovarian cancer cell lines (OVCAR and SKOV-3), in 2D and 3D conditions. Results: The presence of molecular moieties (i.e., mRNAs, lncRNAs) released by these cells to support tissue homeostasis by inhibiting biological processes involved in the etiology of aggressive cancers, as well as to regulate immune pathways at the basis of chronic disorders. Secretome enrichment analysis showed the presence, in both cell lines, of lncRNAs with the predicted function of inhibiting cancer cell proliferation. The exposure of OVCAR and SKOV-3 cells to CM and EXOs revealed a detrimental effect in 2D (by reducing cell viability and inducing apoptosis), and to negatively interfere with spheroid formation in 3D conditions. Conclusion: Data presented here provides molecular insight on the role AF- and CV-MSCs as source of anti-tumor factors, paving the way for the development of therapeutics with the potential to create a pro-regenerative environment for tissue restoration following injury, disease, and cancer. Overall design: To understand the difference in gene expression profiles between mesenchymal stem cells dervived from amniotic fluid vs chorionic villi