Human fetal placental endothelial cells have a mature arterial and a juvenile venous phenotype with adipogenic and osteogenic differentiation potential

Lang, Ingrid; Schweizer, Angela; Hiden, Ursula; Ghaffari-Tabrizi, Nassim; Hagendorfer, Gabriele; Bilban, Martin; Pabst, Maria Anna; Korgun, Emin Türkay; Dohr, Gottfried; Desoyé, Gernot

doi:10.1111/j.1432-0436.2008.00302.x

Cited by 108 publications

(117 citation statements)

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“…29 This enabled us to demonstrate differences in cholesterol efflux from ECs obtained from different sites within one organ, ie, ECs from the placental "barrier" (HPECs) and from the umbilical cord (HUVECs). The present study provides the first evidence for efficient cholesterol efflux at the end of gestation from human ECs of the placenta to lipid-free apolipoproteins and to HDL and identifies contributing mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Human Endothelial Cells of the Placental Barrier Efficiently Deliver Cholesterol to the Fetal Circulation via ABCA1 and ABCG1

Štefulj

Panzenboeck²,

Becker

et al. 2009

Circulation Research

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156

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Abstract-Although maternal-fetal cholesterol transfer may serve to compensate for insufficient fetal cholesterol biosynthesis under pathological conditions, it may have detrimental consequences under conditions of maternal hypercholesterolemia leading to preatherosclerotic lesion development in fetal aortas. Maternal cholesterol may enter fetal circulation by traversing syncytiotrophoblast and endothelial layers of the placenta. We hypothesized that endothelial cells (ECs) of the fetoplacental vasculature display a high and tightly regulated capacity for cholesterol release. Using ECs isolated from human term placenta (HPECs), we investigated cholesterol release capacity and examined transporters involved in cholesterol efflux pathways controlled by liver-X-receptors (LXRs). HPECs demonstrated 2.5-fold higher cholesterol release to lipid-free apolipoprotein (apo)A-I than human umbilical vein ECs (HUVECs), whereas both cell types showed similar cholesterol efflux to high-density lipoproteins (HDLs). Interestingly, treatment of HPECs with LXR activators increased cholesterol efflux to both types of acceptors, whereas no such response could be observed for HUVECs. In line with enhanced cholesterol efflux, LXR activation in HPECs increased expression of ATP-binding cassette transporters ABCA1 and ABCG1, while not altering expression of ABCG4 and scavenger receptor class B type I (SR-BI). Inhibition of ABCA1 or silencing of ABCG1 decreased cholesterol efflux to apoA-I (Ϫ70%) and HDL 3 (Ϫ57%), respectively. Immunohistochemistry localized both transporters predominantly to the apical membranes of placental ECs in situ. Thus, ECs of human term placenta exhibit unique, efficient and LXR-regulated cholesterol efflux mechanisms. We propose a sequential pathway mediated by ABCA1 and ABCG1, respectively, by which HPECs participate in forming mature HDL in the fetal blood. (Circ Res. 2009;104:600-608.)Key Words: maternal-fetal cholesterol transfer Ⅲ endothelial cells Ⅲ HDL Ⅲ liver X receptors C holesterol is indispensable during fetal development. 1 It has been long assumed that most, if not all, cholesterol required for fetal growth is synthesized de novo by the fetus itself, thus making it autonomous from maternal or placental cholesterol supply. However, several lines of evidence have cast doubt on this notion. 2,3 Fetuses that lack the ability to synthesize cholesterol, such as those with the Smith-LemliOpitz syndrome, are, nevertheless, born with low levels of tissue and plasma cholesterol, indicating that they have acquired maternal cholesterol in utero. 4 Recent exciting studies demonstrated a strong correlation between the size and number of atherosclerotic lesions in human fetal arteries with maternal cholesterol levels. 5,6 Moreover, maternal hypercholesterolemia also modified early predictors of cardiovascular disease in the offspring, thus corroborating the concept of developmental programming of adult disease in human. 7 Considering that progression of atherosclerosis in adults takes ages, these striking resu...

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Section: Discussionmentioning

confidence: 99%

Human Endothelial Cells of the Placental Barrier Efficiently Deliver Cholesterol to the Fetal Circulation via ABCA1 and ABCG1

Štefulj

Panzenboeck²,

Becker

et al. 2009

Circulation Research

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156

108

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“…ECs from normal term human placentas were isolated as published earlier [18]. Briefly, after removal of the amnion, arterial chorionic blood vessels at the fetal surface of the chorionic plate were resected.…”

Section: Isolation and Culture Of Placental Ecsmentioning

confidence: 99%

Placental Mesenchymal Stromal Cells Derived from Blood Vessels or Avascular Tissues: What Is the Better Choice to Support Endothelial Cell Function?

König

Weiss

Rossi

et al. 2015

Stem Cells and Development

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Mesenchymal stromal cells (MSCs) are promising tools for therapeutic revascularization of ischemic tissues and for support of vessel formation in engineered tissue constructs. Recently, we could show that avascular-derived MSCs from placental amnion release soluble factors that exhibit survival-enhancing effects on endothelial cells (ECs). We hypothesize that MSCs derived from placental blood vessels might have even more potent angiogenic effects. Therefore, we isolated and characterized MSCs from placental chorionic blood vessels (bv-MSCs) and tested their angiogenic potential in comparison to amnion-derived avascular MSCs (av-MSCs). bv-MSCs express a very similar surface marker profile compared with av-MSCs and could be differentiated toward the adipogenic and osteogenic lineages. bv-MSCs exert immunosuppressive properties on peripheral blood mononuclear cells, suggesting that they are suitable for cell transplantation settings. Conditioned medium (Cdm) from av-MSCs and bv-MSCs significantly enhanced EC viability, whereas only Cdm from bv-MSCs significantly increased EC migration and network formation (Matrigel assay). Angiogenesis array analysis of av-and bv-MSC-Cdm revealed a similar secretion pattern of angiogenic factors, including angiogenin, interleukins-6 and -8, and tissue inhibitors of matrix metalloproteinase-1 and 2. Enzyme-linked immunosorbent assay analysis showed that, in contrast to av-MSCs, bv-MSCs secreted vascular endothelial growth factor. In direct coculture with bv-MSCs, ECs showed a significantly increased formation of vessel-like structures compared with av-MSCs. With regard to therapeutic treatment, bv-MSCs and particularly their Cdm might be valuable to stimulate angiogenesis especially in ischemic tissues. av-MSCs and their Cdm could be beneficial in conditions when it is required to promote the survival and stabilization of blood vessels without the risk of unmeant angiogenesis.

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“…Human placental arterial endothelial cells (HPAECs) were isolated from human term placentae as described previously (31). Briefly, arterial blood vessels were resected from the apical surface of the chorionic plate and washed with HBSS to remove residual blood.…”

Section: Isolation Of Primary Third-trimester Human Placental Arteriamentioning

confidence: 99%

Macrophage-Derived IL-33 Is a Critical Factor for Placental Growth

Fock

Mairhofer

Otti

et al. 2013

The Journal of Immunology

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IL-33, the most recently discovered member of the IL-1 superfamily and ligand for the transmembrane form of ST2 (ST2L), has been linked to several human pathologies including rheumatoid arthritis, asthma, and cardiovascular disease. Deregulated levels of soluble ST2, the natural IL-33 inhibitor, have been reported in sera of preeclamptic patients. However, the role of IL-33 during healthy pregnancy remains elusive. In the current study, IL-33 was detected in the culture supernatants of human placental and decidual macrophages, identifying them as a major source of secreted IL-33 in the uteroplacental unit. Because flow cytometry and immunofluorescence stainings revealed membranous ST2L expression on specific trophoblast populations, we hypothesized that IL-33 stimulates trophoblasts in a paracrine manner. Indeed, BrdU incorporation assays revealed that recombinant human IL-33 significantly increased proliferation of primary trophoblasts as well as of villous cytotrophoblasts and cell column trophoblasts in placental explant cultures. These effects were fully abolished upon addition of soluble ST2. Interestingly, Western blot and immunofluorescence analyses demonstrated that IL-33 activates AKT and ERK1/2 in primary trophoblasts and placental explants. Inhibitors against PI3K (LY294002) and MEK1/2 (UO126) efficiently blocked IL-33–induced proliferation in all model systems used. In summary, with IL-33, we define for the first time, to our knowledge, a macrophage-derived regulator of placental growth during early pregnancy.

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Human fetal placental endothelial cells have a mature arterial and a juvenile venous phenotype with adipogenic and osteogenic differentiation potential

Cited by 108 publications

References 50 publications

Human Endothelial Cells of the Placental Barrier Efficiently Deliver Cholesterol to the Fetal Circulation via ABCA1 and ABCG1

Human Endothelial Cells of the Placental Barrier Efficiently Deliver Cholesterol to the Fetal Circulation via ABCA1 and ABCG1

Placental Mesenchymal Stromal Cells Derived from Blood Vessels or Avascular Tissues: What Is the Better Choice to Support Endothelial Cell Function?

Macrophage-Derived IL-33 Is a Critical Factor for Placental Growth

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