Decidual mesenchymal stem/stromal cells from preeclamptic patients secrete endoglin, which at high levels inhibits endothelial cell attachment invitro.

Autor: Perera C; University of Melbourne Department of Obstetrics and Gynaecology, Royal Women's Hospital, Parkville, Victoria, 3052, Australia; Pregnancy Research Centre, Department of Maternal-Fetal Medicine, Royal Women's Hospital, Parkville, Victoria, 3052, Australia., Zheng S; University of Melbourne Department of Obstetrics and Gynaecology, Royal Women's Hospital, Parkville, Victoria, 3052, Australia; Pregnancy Research Centre, Department of Maternal-Fetal Medicine, Royal Women's Hospital, Parkville, Victoria, 3052, Australia., Kokkinos MI; Pregnancy Research Centre, Department of Maternal-Fetal Medicine, Royal Women's Hospital, Parkville, Victoria, 3052, Australia., Georgiou HM; University of Melbourne Department of Obstetrics and Gynaecology, Royal Women's Hospital, Parkville, Victoria, 3052, Australia; Pregnancy Research Centre, Department of Maternal-Fetal Medicine, Royal Women's Hospital, Parkville, Victoria, 3052, Australia., Schoppet M; Exopharm Ltd, Level 17, 31 Queen Street, Melbourne, VIC, 3000, Australia., James PF; Exopharm Ltd, Level 17, 31 Queen Street, Melbourne, VIC, 3000, Australia., Brennecke SP; University of Melbourne Department of Obstetrics and Gynaecology, Royal Women's Hospital, Parkville, Victoria, 3052, Australia; Pregnancy Research Centre, Department of Maternal-Fetal Medicine, Royal Women's Hospital, Parkville, Victoria, 3052, Australia., Kalionis B; University of Melbourne Department of Obstetrics and Gynaecology, Royal Women's Hospital, Parkville, Victoria, 3052, Australia; Pregnancy Research Centre, Department of Maternal-Fetal Medicine, Royal Women's Hospital, Parkville, Victoria, 3052, Australia. Electronic address: bill.kalionis@thewomens.org.au.
Jazyk: angličtina
Zdroj: Placenta [Placenta] 2022 Aug; Vol. 126, pp. 175-183. Date of Electronic Publication: 2022 Jul 07.
DOI: 10.1016/j.placenta.2022.07.003
Abstrakt: Introduction: In preeclampsia (PE), inadequate remodelling of spiral arterioles in the decidua basalis causes oxidative stress and subsequent increased release of antiangiogenic soluble endoglin (sENG) into the maternal circulation. Decidual mesenchymal stem/stromal cells (DMSCs) reside adjacent to endothelial cells in this vascular niche. Surprisingly, DMSCs express membrane-bound ENG (CD105). PE-affected DMSCs (PE-DMSCs) are abnormal and due to reduced extravillous invasion, more of them are present, but the significance of this is not known.
Methods: DMSCs were isolated and characterised from normotensive control and severe-PE placentae. Extracellular vesicle (EV) types, shed microvesicles (sMV) and exosomes, were isolated from DMSC conditioned media (DMSC CM ), respectively. Secretion of ENG by DMSCs was assessed by ELISA of DMSC CM , with and without EV depletion. The effects of reducing ENG concentration, by blocking antibody, on human umbilical vein endothelial cell (HUVEC) attachment were assessed by xCELLigence real-time functional assays.
Results: ENG was detected in DMSC CM and these levels significantly decreased when depleted of exosomes and sMV. There was no significant difference in the amount of ENG secreted by control DMSCs and PE-DMSCs. Blocking ENG in concentrated DMSC CM , used to treat HUVECs, improved endothelial cell attachment.
Discussion: In normotensive pregnancies, DMSC secretion of ENG likely has a beneficial effect on endothelial cells. However, in PE pregnancies, shallow invasion of the spiral arterioles exposes more PE-DMSC derived sources of ENG (soluble and EV). The presence of these PE-DMSCs in the vascular niche contributes to endothelial cell dysfunction.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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