Modeling defects in trophoblast differentiation using Trisomy 21-affected human pluripotent stem cells

Abstract

s / Placenta 35 (2014) A1eA112 A10 Methods: miR-218 levels were assessed with real time PCR in tissues collected from healthy and PE patients. Invasion andmigration of EVTs was studied in the HTR-8/SVneo trophoblast cell line and first trimester placenta. The switch to an endothelial adhesion molecule phenotype was measured with VE-Cadherin, CD31 as well as integrin a5b1, a1b1 and aVb3 mRNA levels in first trimester placentas. Finally, an in vitro model of spiral artery remodelling was used to further investigate the role of miR-218 in EVT differentiation, invasion and remodelling of the maternal vasculature. Results:miR-218 was expressed in placenta throughout pregnancy and its level was significantly down-regulated in placenta obtained from patients with PE as compared to gestational age-matched controls. miR-218 mimic promoted, while anti-miR-218 suppressed, the outgrowth of EVTs as well as migration and invasion in vitro. Dissected placental columns treated with miR-218 mimic showed an increase in all of these endothelial markers. Immunohistochemistry analysis revealed accelerated spiral artery remodelling and more invasive EVTs in the miR218 treated samples. Conclusion: Taken together, these novel findings suggest that miR-218 promotes trophoblast migration, invasion and differentiation into endovascular EVTs required for proper spiral artery remodelling. NI.8. MODELING DEFECTS IN TROPHOBLAST DIFFERENTIATION USING TRISOMY 21-AFFECTED HUMAN PLURIPOTENT STEM CELLS Mariko Horii , Younghan Kim , Yingchun Li , Mina Lee , Karen Sabatini , Louise C. Laurent , Ying Liu , Mana M. Parast a Department of Pathology, University of California San Diego, La Jolla, California, USA; Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Severance Hospital, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Obstetrics and Gynecology ,College of Medicine, Chungnam National University, Daejeon, Republic of Korea; Department of Reproductive Medicine, University of California San Diego, La Jolla, California, USA; Department of Neurosurgery, Medical School, Houston, Texas, USA; Center for Stem Cell and Regenerative Medicine Senator Lloyd and B.A. Bentsen Center for Stroke Research The Brown Foundation Institute of Molecular Medicine The University of Texas Health Science Ce,