Self‐assembled human placental model from trophoblast stem cells in a dynamic organ‐on‐a‐chip system

The placental barrier plays a key role in protecting the developing fetus from xenobiotics and exchanging substances between the fetus and mother. However, the trophoblast cell lines and animal models are often inadequate to recapitulate the key architecture and functional characteristics of human p...

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Veröffentlicht in:Cell proliferation Jg. 56; H. 5; S. e13469 - n/a
Hauptverfasser: Cao, Rongkai, Wang, Yaqing, Liu, Jiayue, Rong, Lujuan, Qin, Jianhua
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England John Wiley & Sons, Inc 01.05.2023
John Wiley and Sons Inc
Schlagworte:
Animal models
Animals
Biochips
Biomimetics
Cell culture
Cell Differentiation
Cell lines
Chorionic gonadotropin
Chorionic Gonadotropin - analysis
Chorionic Gonadotropin - metabolism
Chorionic Gonadotropin - pharmacology
Collagen
Endocrine disruptors
Endothelial cells
Endothelial Cells - metabolism
Endothelium
Epithelium
External stimuli
Female
Fetuses
Fluid flow
Gene expression
Glucose transport
Gonadotropins
Humans
Microphysiological Systems
Original
Permeability
Pituitary (anterior)
Placenta
Placenta - metabolism
Pregnancy
RNA transport
Scanning electron microscopy
Self-assembly
Signal transduction
Stem Cells
Structure-function relationships
Toxicants
Trophoblasts - metabolism
Xenobiotics
ISSN:0960-7722, 1365-2184, 1365-2184
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Zusammenfassung:The placental barrier plays a key role in protecting the developing fetus from xenobiotics and exchanging substances between the fetus and mother. However, the trophoblast cell lines and animal models are often inadequate to recapitulate the key architecture and functional characteristics of human placental barrier. Here, we described a biomimetic placental barrier model from human trophoblast stem cells (hTSCs) in a perfused organ chip system. The placental barrier was constructed by co‐culture of hTSCs and endothelial cells on the opposite sides of a collagen‐coated membrane on chip. hTSCs can differentiate into cytotrophoblasts (CT) and syncytiotrophoblast (ST), which self‐assembled into bilayered trophoblastic epithelium with placental microvilli‐like structure under dynamic cultures. The formed placental barrier displayed dense microvilli, higher level secretion of human chorionic gonadotropin (hCG), enhanced glucose transport activity. Moreover, RNA‐seq analysis revealed upregulated ST expression and activation of trophoblast differentiation‐related signalling pathways. These results indicated the key role of fluid flow in promoting trophoblast syncytialization and placental early development. After exposure to mono‐2‐ethylhexyl phthalate, one of the endocrine disrupting chemicals, the model showed inhibited hCG production and disturbed ST formation in trophoblastic epithelium, suggesting impaired placental structure and function elicited by environmental toxicants. Collectively, the hTSCs‐derived placental model can recapitulate placenta physiology and pathological response to external stimuli in a biomimetic manner, which is useful for the study of placental biology and associated diseases. Human placental barrier is consisted of trophoblastic layer, basal lamina, and the fetal capillaries in vivo. We developed a biomimetic placental barrier‐on‐a‐chip model by self‐assembly of human trophoblast stem cells in a dynamic microenvironment, recapitulating the key architecture and functions of human placental villi.
Bibliographie:Rongkai Cao and Yaqing Wang contributed equally to this work.
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ISSN:0960-7722
1365-2184
1365-2184
DOI:10.1111/cpr.13469