Healthy and diseased placental barrier on-a-chip models suitable for standardized studies

Gwenaëlle Rabussier, Ivan Bünter, Josse Bouwhuis, Camilla Soragni, Torben van Zijp, Chee Ping Ng, Karel Domansky, Leon J. de Windt, Paul Vulto, Colin E. Murdoch, Kristin M. Bircsak, Henriëtte L. Lanz (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)
48 Downloads (Pure)

Abstract

Pathologies associated with uteroplacental hypoxia, such as preeclampsia are among the leading causes of maternal and perinatal morbidity in the world. Its fundamental mechanisms are yet poorly understood due to a lack of good experimental models. Here we report an in vitro model of the placental barrier, based on co-culture of trophoblasts and endothelial cells against a collagen extracellular matrix in a microfluidic platform. The model yields a functional syncytium with barrier properties, polarization, secretion of relevant extracellular membrane components, thinning of the materno-fetal space, hormone secretion, and transporter function. The model is exposed to low oxygen conditions and perfusion flow is modulated to induce a pathological environment. This results in reduced barrier function, hormone secretion, and microvilli as well as an increased nuclei count, characteristics of preeclamptic placentas. The model is implemented in a titer plate-based microfluidic platform fully amenable to high-throughput screening. We thus believe this model could aid mechanistic understanding of preeclampsia and other placental pathologies associated with hypoxia/ischemia, as well as support future development of effective therapies through target and compound screening campaigns.

Statement of Significance: The human placenta is a unique organ sustaining fetus growth but is also the source of severe pathologies, such as Preeclampsia. Though leading cause of perinatal mortality in the world, preeclampsia remains untreatable due to a lack of relevant in vitro placenta models. To better understand the pathology, we have developed 3D placental barrier models in a microfluidic device. The platform allows parallel culture of 40 perfused physiological miniaturized placental barriers, comprising a differentiated syncytium and endothelium that have been validated for transporter functions. Exposure to a hypoxic and ischemic environment enabled the mimicking of preeclamptic characteristics in high-throughput, which we believe could lead to a better understanding of the pathology as well as support future effective therapies development.

Original languageEnglish
Pages (from-to)363-376
Number of pages14
JournalActa Biomaterialia
Volume164
Early online date26 Apr 2023
DOIs
Publication statusPublished - 1 Jul 2023

Keywords

  • disease modeling
  • preeclampsia
  • maternal-fetal interface
  • standardized
  • organ-on-a-chip
  • Maternal-fetal interface

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Biotechnology
  • Biomedical Engineering
  • Biomaterials

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