A Novel Three‐Dimensional <i>In Vitro</i> System to Study Trophoblast–Endothelium Cell Interactions

Aldo, Paulomi; Krikun, Graciela; Visintin, Irene; Lockwood, Charles; Romero, Roberto; Mor, Gil

doi:10.1111/j.1600-0897.2007.00493.x

Cited by 60 publications

(61 citation statements)

References 35 publications

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“…For example, another human EVT cell line TCL1 formed endothelial-like tubes on GFR matrigel [50][51][52]. In another report, the present EVT cell line was found to form sparse or no tubes on matrigel when cultured alone; however, in the presence of endothelial cells, they collaborated and synchronized with endothelial cells, forming capillary-like networks [47]. Other studies similar to the present have shown that EVT cell lines have the intrinsic capacity to form tubes on matrigel, which can be stimulated by various decidua-derived factors including EG-VEGF [53], CTGF [54], and products of .…”

Section: Discussionmentioning

confidence: 90%

“…During arterial remodeling, EVT cells acquire a phenotype that mimics cells of the vascular system, particularly endothelial cells [46]. This change in phenotype, often referred to as endovascular differentiation, includes expression of vascular endothelial markers such as VEcadherin, platelet endothelial cell adhesion molecule-1, vascular cell adhesion molecule-1, and integrin aVb3 [46], and the ability to mimic the tube-forming behavior of endothelial cells in vitro upon culture on matrigel [37,[47][48][49].…”

Section: Discussionmentioning

confidence: 98%

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Mechanisms in Decorin Regulation of Vascular Endothelial Growth Factor-Induced Human Trophoblast Migration and Acquisition of Endothelial Phenotype1

Lala

Girish

Cloutier-Bosworth

et al. 2012

Biology of Reproduction

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Extravillous trophoblast (EVT) cells of the human placenta invade the uterine decidua and utero-placental arteries to establish an efficient exchange of key molecules between maternal and fetal blood. Trophoblast invasion is stringently regulated in situ both positively and negatively by a variety of factors at the fetal-maternal interface to maintain a healthy utero-placental homeostasis. One such factor, decorin, a transforming growth factor (TGF)-beta binding, leucine-rich proteoglycan produced by the decidua, negatively regulates EVT proliferation, migration, and invasiveness independent of TGF-beta. We reported that these decorin actions were mediated by its binding to multiple tyrosine kinase receptors, including vascular endothelial growth factor receptor (VEGFR)-2. The present study explores the mechanisms underlying decorin antagonism of VEGF (VEGF-A) stimulation of endovascular differentiation of EVT using our EVT cell line, HTR-8/SVneo. We observe that decorin inhibits VEGF-induced EVT cell migration and endothelial-like tube formation on matrigel. VEGF activates MAPKs (p38 MAPK, MEK3/6, and ERK1/2) in EVT cells, and the activation is blocked in both cases by decorin. Employing selective MAPK inhibitors, we show that both p38 and ERK pathways contribute independently to VEGF-induced EVT migration and capillary-like tube formation. VEGF upregulates the vascular endothelial (VE) markers VE-cadherin and beta-catenin in EVT and endothelial cells, and this upregulation is blocked by decorin and MAPK inhibitors. These results suggest that decorin inhibits VEGF-A stimulation of trophoblast migration and endovascular differentiation by interfering with p38 MAPK and ERK1/2 activation. Thus decorin-mediated dual impediment of endovascular differentiation of the EVT and angiogenesis may have implications for pathogenesis of preeclampsia, a hypoinvasive trophoblast disorder in pregnancy.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 98%

Mechanisms in Decorin Regulation of Vascular Endothelial Growth Factor-Induced Human Trophoblast Migration and Acquisition of Endothelial Phenotype1

Lala

Girish

Cloutier-Bosworth

et al. 2012

Biology of Reproduction

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“…11 The use of 3-dimensional (3D) spheroid cell culture models may overcome some limitations of both monolayer cells and ex vivo explants in studying the initial stages of human placentation, as cells grown in 3D cultures retain a phenotype more similar to in vivo than in monolayer. 18 Vascular spheroids show some of the phenotypic properties of vessels, such as differentiation of EC as demonstrated by a downregulation of platelet-derived growth factor expression, CD34 expression, and a reduction in apoptosis.…”

Section: E94 Arterioscler Thromb Vasc Biol March 2013mentioning

confidence: 99%

“…Previous models include the use of monolayer cocultures, 7 explant cultures, 8 and endothelial capillary tubes on Matrigel. 9 These have revealed the secretion of a number of factors by endovascular trophoblast which impact on the physiological changes that occur in SA remodeling, including the secretion of proteases to degrade the extracellular matrix and disrupt cellular interactions, 10 and chemokines including interleukin (IL)-8, MCP-1, 11 and IL-6. 12 Trophoblast also induce reduced expression and disruption of EC adhesion molecules, such as E-cadherin, 13 and apoptosis of vascular cells.…”

mentioning

confidence: 99%

Trophoblast-Induced Changes in C-X-C Motif Chemokine 10 Expression Contribute to Vascular Smooth Muscle Cell Dedifferentiation During Spiral Artery Remodeling

Wallace

Cartwright

Begum

et al. 2013

ATVB

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Objective-During pregnancy, fetal trophoblast disrupt endothelial cell and vascular smooth muscle cell (VSMC) interactions in spiral arteries of the maternal decidua to enable increased nutritional and oxygen delivery to the fetus. Little is known regarding this transformation because of difficulties of studying human pregnancy in vivo. This study investigated how trophoblast-secreted factors affect the interactions of vascular cells and the differentiation status of VSMC during spiral arteries remodeling using 3-dimensional vascular spheroid coculture. Methods and Results-Endothelial cell and VSMC were cocultured in hanging droplets to form spheroids representing an inverted vessel lumen. Control or conditioned media from an extravillous trophoblast (EVT) cell line was incubated with vascular spheroids for 24 hours. Spheroid RNA was then analyzed by Illumina Sentrix BeadChip array. Spheroids incubated with EVT conditioned medium showed significant up/downregulation of 101 genes (>1.5-fold; P<0.05), including an upregulation of C-X-C motif chemokine 10 (IP-10). C-X-C motif chemokine 10 expression was confirmed by qualitative real-time PCR and Western blot analysis of spheroids, and immunohistochemistry of first trimester decidua and ex vivo dissected nonplacental bed spiral arteries. EVT conditioned medium reduced VSMC expression of differentiation markers, and both EVT conditioned medium and C-X-C motif chemokine 10 increased motility of VSMC indicating dedifferentiation of VSMC. Conclusion-EVT-induced

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“…We and others have recently developed a three-dimensional culture system on Matrigel that mimics endovascular cross-talk between trophoblast cells and endothelial cells (44,45). We carried out trophoblast-endothelial cells interactions on Matrigel in the absence or presence of Aroclor 1254, AQP1 blocking antibody, or Aroclor 1254 and estradiol.…”

Section: Inhibition Of Endovascular Interactions Between Trophoblastsmentioning

confidence: 99%

The Water Channel Aquaporin 1 Is a Novel Molecular Target of Polychlorinated Biphenyls for in Utero Anomalies

Tewari

Kalkunte

Murray

et al. 2009

Journal of Biological Chemistry

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A Novel Three‐Dimensional In Vitro System to Study Trophoblast–Endothelium Cell Interactions

Cited by 60 publications

References 35 publications

Mechanisms in Decorin Regulation of Vascular Endothelial Growth Factor-Induced Human Trophoblast Migration and Acquisition of Endothelial Phenotype1

Mechanisms in Decorin Regulation of Vascular Endothelial Growth Factor-Induced Human Trophoblast Migration and Acquisition of Endothelial Phenotype1

Trophoblast-Induced Changes in C-X-C Motif Chemokine 10 Expression Contribute to Vascular Smooth Muscle Cell Dedifferentiation During Spiral Artery Remodeling

The Water Channel Aquaporin 1 Is a Novel Molecular Target of Polychlorinated Biphenyls for in Utero Anomalies

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