Khanabdali, R and Zheng, S and Melton, PE and Georgiou, HM and Moses, E and Brennecke, SP and Kalionis, B, Late/post-term decidual basalis-derived mesenchymal stem/stromal cells show evidence of advanced ageing and downregulation of microRNA-516b-5p, Placenta, 109 pp. 43-54. ISSN 0143-4004 (2021) [Refereed Article]
© 2021 Elsevier Ltd. All rights reserved.
Introduction: The placenta is a short-lived organ, yet it shows signs of progressive ageing in the third trimester. Studies of ageing chorionic placental tissue have recently flourished, providing evidence of advanced ageing of tissues in the late/post-term (L/PT) period of gestation. However, ageing of the maternal aspect of the maternal-fetal interface, specifically the decidua basalis, is poorly understood. Here, we investigated whether the L/PT period was associated with advanced ageing and exhaustion of important decidua basalis mesenchymal stem/stromal cells (DMSCs) functions.
Methods: In this study, DMSCs were isolated and characterised from early term (ET) and L/PT placental tissue and they were then investigated by employing various MSC potency and ageing assays. RNA sequencing was also performed to screen for specific microRNAs that are associated with stem cell exhaustion and ageing between ET- and L/PT-DMSCs.
Results: L/PT-DMSCs, when compared to ET-DMSCs, showed significantly lower cell proliferation and a significant higher level of cell apoptosis. L/PT-DMSCs showed significantly lower resistance to oxidative stress and a significant decrease in antioxidant capacity compared with ET-DMSCs. Western blot analysis revealed increased expression of the stress-mediated P-p38MAPK protein in L/PT-DMSCs. RNA Sequencing showed microRNA (miR) miR-516b-5p, was present at significantly lower levels in L/PT-DMSCs. Inhibition of miR-516b-5p in ET-DMSCs revealed a decline in the ability of the inhibited cells to survive in extended cell culture.
Discussion: These data provide the first evidence of advanced ageing and exhaustion of important stem cell functions in L/PT-DMSCs, and the involvement of specific miRs in the DMSC ageing process.
|Item Type:||Refereed Article|
|Keywords:||Decidua basalis, MSCs, placenta ageing, pregnancy, microRNAs|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Reproductive medicine|
|Research Field:||Obstetrics and gynaecology|
|Objective Group:||Specific population health (excl. Indigenous health)|
|Objective Field:||Women's and maternal health|
|UTAS Author:||Melton, PE (Dr Phillip Melton)|
|UTAS Author:||Moses, E (Professor Eric Moses)|
|Deposited By:||Menzies Institute for Medical Research|
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